Viewpoint canceration mode horizontal cells

Human exploration of the cancer problem has gone through a century of time. With the advancement of science and technology, the most serious risks to human health diseases have been uniform, but deadly to cancer is the same, and have highlighted one of the medical challenges today. Although the cancer problem affects millions of heart, scientists are trying to expose the crux of the problem, but for a long time and did not achieve the fundamental breakthroughs. Why?, in General, there is no understanding of the true meaning of carcinogenesis principle. Once you have a clear understanding of how cancer cells cancer problem solve it soon.

First, look for breakthrough

For problem-solving pressing, for a long time many scientists under the respective observation and research, has made a number of hypotheses to explain the principle of carcinogenesis, such as Chemical carcinogenesis hypothesis, physical factors cause cancer hypothesis, endocrine hypothesis, virus cancer hypothesis, and so on. Unfortunately, most of all in these hypothesis only stay in phenotypic change level. Molecular biology and molecular genetics of basic principle tells us that the cells property is present in the nucleus of the genetic basis of substances — deoxyribonucleic acid (shorthand for DNA), DNA contains all the required biological gene, different genes in accordance with the normal "timetable" and the "drawings" in the expression activities that produce a specific protein products, then these proteins to exercise specific physiological functions, and thus constitute a certain genetic characteristics. From this concept started in 1969 was raised "carcinogenic genes hypothesis", that should exist in cells can cause cancer genes, when the cells to the outside world and the role of carcinogenic factors after the gene will be activated and activities and produce cancer protein, eventually the carcinogenesis. There is no doubt that this hypothesis is very attractive because it stood at the gene level application logic reasoning be seen in the tumor. Because the genes determine certain genetic characteristics and tumor but is a variation of genetic characteristics, so there should be a corresponding gene determines such variation in genetic characteristics, this is a cancer gene. This reasoning is tenable, and refreshing. Unfortunately due to time limitations of the theory and techniques, scientists are very difficult to carry out gene level. Since the 1970s, as the frontiers of biological science — the rapid development of molecular biology, in particular genetic engineering (also called genetic engineering) technology development and even better, a cancer molecular biologists may adopt gene isolation, transfer and transfer of technology, DNA recombination technology, genetic fingerprinting techniques and DNA sequencing technologies and gene expression in detection technology and other modern technologies directly at gene level, on the existence of cancer genes, which makes cancer research level raised to a higher level, opened a new molecular biology of cancer.

Scientists were materialists. In the face of the vastness of the biological world, where to find cancer gene? here need realistic spirit and creative thinking. Means to face the facts, classification, comparison and synthesis, identify the breakthrough, in order to run, hit the nail on the head. The high biological cell genome size is too big (it contains the number of genes 106 orders of magnitude), and guess the number of cancer genes could not possibly many, its genome, proportional to the minimal, few can be ignored, so the use of such cells as separation and identification of cancer gene material, like a needle in the haystack, laborious and reactive, it is clear that the road is blocked. Scientists to focus on the retrovirus, this virus genome very simple, only with three, five genes, each on virus replication required-gene structure and restriction enzyme Atlas also clearer, more important is the carcinogenicity of these viruses have been identified. Therefore, in accordance with the "cancer genes hypothesis", from this virus genome in cancer gene should be able to successfully and is the most simple and direct way. Sure enough, after much effort, in 1976, the first oncogene-Src gene — separation was a success. Src gene Rous Sarcoma virus, in chicken is responsible for induced carcinogenesis of gene, cell culture system enables NIH3T3 cells (malignant change) and maintenance of the State, to be transformed into cells in the nude, born sarcoma. Since then, continuous from other retrovirus isolated from different cancer genes, so far, a total of 24, all of which are in a single copy. The facts have proven that breakthrough retrovirus as successfully separating out the cancer gene, is thinking logic and thinking the art of victory, this put in place the three characteristics of creative thinking, this kind of thought process from specific routes to make people work goes through possession of material, analysis of comparative material, the development of research programmes to achieve results on the road; in the know, the people developed from diverse complex phenomena by vague concept gradually get clear conclusions of transition.

Breakthrough is turned on, the next goal is to prove that the human and other higher vertebrate cells also exists cancer gene, which is built to cancer gene-centric carcinogenesis principle mode of the first step. This step is easier to move because of retroviral oncogenes provides ideal probe, the probe is equivalent to an easy recognition and detection of signals, people can track its whereabouts, so long as these probes and human DNA Molecular hybridization, can detect these DNA are also contain cancer gene, results expected, the date in the animal cells have been identified, where retroviral oncogene in, they also possessed, in human cells has identified a dozen or so.

Human and animal cells in cancer gene facts carcinogenesis study on the principle of the new dawn, but also brought more and more complex problems, and even have some pitfalls. On the one hand, because of the cancer gene discovery, enabling various phenotypic change based on hypotheses and opinions on the gene level, which allows understanding the essence of the phenomenon to a step forward. On the other hand, considering the cancer gene's role in carcinogenesis, because of the existence and activities of the former is not isolated, so you must consider the regulation of gene expression and activity of activated and expression products on cells due to the effects of multiple enzyme system problems, gene level demonstrate carcinogenesis original

Reason than the single-table from the form or to consider much more complex and more difficult, consider factors also have a finer decomposition. This perhaps is the scientific study of thinking, this feedback feedback main variables complicated and separability and doubt increased (i.e. use suspected method) of the original form has been simplified or seems easy conclusions also tends to be more complex, causing new problems. However, this kind of feedback also provides new information: once you pass through new difficulties, away from the truth. To do this, we may wish to present relevant cancer gene study of complex situations and some major difficulties.

Second, with regard to cancer gene activation mechanism

Normal cells oncogene does exist, specifically, the cancer gene and everyone has had cancer, but a handful who after all, this description in General cancer gene is not active. It was observed that, in the normal cells in cancer gene expression of extremely low or even detect it, and in cancer cells in a cancer gene expression amount to tens of hundreds of times, if not a cancer gene is activated, is unthinkable. It seems that cell cancer first need to activate the expression of oncogenes. Therefore the relevant oncogenes in recent years, mostly for cancer gene activation principle, the documentation very much, but on each of the proposed mechanism also exist in some of the evidence, therefore each activation mechanism in carcinogenesis in status remains worth exploring.

Initially proposed a cancer gene activation mechanism called promoting child (promoter) into carcinogenic mode. The pattern is of the view that the virus as long as is famous for its promotion of the child contained in the inserted into cells oncogene upstream area, you can start the cancer gene expression out of them, insert the location above to cancer genes, too much is invalid. People infected with a virus and not less, but the virus inserts to promote child just beside the chance that oncogene is rather small, it generally does not cause cancer. Later discovered many experimental facts with this mechanism cannot be interpreted, such as mice Lymphoma virus promote child you can insert many points, but not necessarily directly at the cancer gene upstream area adjacent; lymphoma cells in promoting child exactly though virus into cancer-myc upstream adjacent, but this gene does not increase expression; in some cases, the virus inserts for the child to stay away from cancer gene of resting, but also activated oncogenes. Therefore, ISO-insert, insert promoting child probably carcinogenic mode is only one kind of explanation. For other different experimental evidence, there is no better explanation of the pattern given. Some people think that, regardless of what location, with insert-inserts can be regarded as mutagens it by changing the regulatory sequences area nucleosome or location and chromatin structure, so that the cancer gene and promoting expression factor near and combined with the result that its expression.

Some authors to consider focusing on the structure of the gene itself. That in normal cells and cancer gene is a proto-oncogene state exists, probably via point mutations of stimulation start activation, becomes a lively cancer gene. At the end of 1982, there are two laboratories in each block messages from two patients with bladder cancer cells in separating out the expression of oncogenes C-Ha-rasl, by comparison with normal cells and found the former C-Ha-rasl 12th codon mutation has occurred, so that the original encoding of glycine password change as encoded valine, their results are, immediately caused a stir in the international Oncology scholars, it is said that these two work also won the prize. This theory is based on the identified mutation theory. Cancer causes of mutation theory is an old theory, long before they come, but has no direct evidence, the discovery of molecules, for the first time as a mutation theory provides the molecular basis. Usually that C-Ha-rcsl 12th password is located a short sequence includes Guanosine triphosphate (GTP) binding sites, under normal conditions, the site above cover with regulatory proteins, the protein hampered the GTP and GTP binding sites, so that it cannot express. The sequence occurred, due to the changed the GTP binding sites of structure, apart from the regulatory proteins, that can be combined with GTP, thereby activating cancer gene. On this interpretation is also suggested to suspect and obtain evidence of the correctness of such doubt. It was confirmed that, in the same patients with bladder cancer, bladder cancer cells and normal cells and white blood cell, C-Ha-rasl 12th codon have undergone the same point mutations. This result makes many people raised the question of the ras oncogene mutations is just a polymorphism? gene polymorphism is common in nature genetics, polymorphism is neutral mutations of genes, and not on gene function has no effect. Now that some of the cancer gene polymorphism do exist, but they appear less frequently. As for the cancer gene polymorphism is the cancer cancer factors become sensitive, there is as yet unknown.

Cancer gene reflow, including insert, missing, translocation and amplification, they might be activated oncogenes. In human Birket lymphoma and mice oar cell tumors, cancer genes by translocation to the IgG heavy chain gene region, but such translocation is how to make cancer gene resurrection is controversial. Some authors think are the oncogene translocations after borrowing immunoglobulin of efficient promoter; some believe that is affected by the distance of Enhancer (en-hancer) stimulus; some are thought to be caused by cancer gene translocations from pre-existing blind promoter role. These reasons are causing excessive cancer gene expression. However, some authors do not meet the above explanation, they think that since gene rearrangement of forms you can diversify, its activation mechanism should diversify, sure enough, later discovered some tumor cells oncogene translocations in place and not immunoglobulin gene region, but other places. Sometimes the cancer gene in the genome in a cell does not happen, but can translocation in different locations on a large number of amplification (called gene amplification) so that it is normally a single copy of the changes to multiple copies, so that the expression product to increase the corresponding multiples. Sometimes the cancer gene may gene partially missing or inserted and activated. Have the authors emphasize that activate class

-That the deletion and insertion will make the cancer gene produce structural abnormalities of the product, they are truly cancerous proteins. However, to date, the cancer gene rearrangement, what these rearrangements is changed the cancer gene structure dominated or enhance its expression dominant still cannot be conclusive.

Collaboration on cancer gene, is an argument from a new things, new ideas. Issues surrounding cancer gene, the start argument and debate appears one of the key issues are how to use NIH3T3 cells. 3T3 cells are mouse fibroblasts, rodent culture into lines, but in the cultivation of many generations, they gradually lost its normal cells, the transition to the malignant direction but has not reached the level of malignant cells. Therefore, this cell is not normal cells, the cells as identification of cancer gene test system is not perfect, it cannot be a true description of the cancer gene's role in normal cells and its role in carcinogenesis. In addition, in humans or animals, cancer growth with tissues and cell type-specific 3T3 cell lines, with identification of cancer genes but not illustrate this point, this constitutes a not consistent with the facts. Plus, from clinical and pathological process of cancer, cancer requires a long development process, including pre-cancerous (hyperplasia), cancer and cancer formation period. In accordance with this timetable, there is reason to believe that cell carcinogenesis is not to say that the variable is the same, but after many changes in the process is completed in stages. This fact is due to the cells in the treatment of foreign environment hazards or unexpected factors make mistakes, the mistakes and the vicious circle of cumulative result of can also be considered is changeing process. Based on this speculation, many people think that, in order to reflect the cancer gene to normal cells the role of cancer, should be based on normal primary cells or second-generation cultured cells as experimental system. For these ideas, someone has designed a set of experimental programme, got very meaningful results: bladder cancer cell line with EJ's cancer gene C-Ha-rasl can easily make 3T3 cell transformation, if the second generation of swapping the normal embryonic fibroblasts REF, you cannot place transformation, it not only describes the 3T3 and REF in nature, but also in normal cells in a single C-Ha-rasl is insufficient to cause cancer. Myc oncogene also ibid. The author further C-Ha-rasl and myc together with the culture of REF, miracle: a transformation of REF, transforming the REF can bare the subcutaneous tumors induced by. This result shows the collaboration between cancer gene may be a normal cell carcinoma. This discovery has changed in the past on carcinogenesis principle is only considered the role of a single gene, the experimental system closer to the natural state. Later also found many tumor formation and activation of ras and myc expression, according to this view was expressed that the cancer gene and does not have an organization-specific, so different tumors occur through the same mechanism that is the same kind of cancer gene activation. Collaboration in cancer gene, different cancer genes activated mode and time of the order, which in turn support the carcinogenesis of multi-stage theories. Collaboration in cancer gene, different cancer gene function is different in order to achieve a division of collaboration. If ras is responsible for cancer, but it is not sufficient to make the carcinogenesis, once the myc is activated it will make the cells for cloning advantage, the formation of uncontrolled proliferation of cell lines, the ras-induced carcinogenesis function adequately. We cannot think that the problem has been resolved. It has been suggested that this system involves two cancer gene's role, therefore, at best, only two-stage carcinogenesis description. In fact, many system tumor formation is clearly more than two stages, as carcinogenesis process than the fibroblast cell carcinogenesis is longer and more complex. In the latter case, what is involved with the collaboration of oncogenes? also, cancer, multiple stage process must participate in a variety of cancer genes? the existence of oncogenes and other factors of collaboration possibilities, although these issues? "in order to extend the above results, but seems to be better than the results of the experiment itself makes people think deeply.

It was a surprise that certain cancer gene makes the products from the cell surface to pass information to another cancer gene makes its resurrection, cause carcinogenesis and experimental proof of the existence of such a mechanism, due to the effects of the program is started from the film, the last to reach the cell nucleus is the function called sequential carcinogenic effect.

Here also mentioned "guerrilla mechanism". As we all know, the herpes simplex virus can cause cell transformation, and cervical cancer relationship is very high. But for a long time, it is very difficult to find the virus in cancer cells of the bead wire horse track, how they are causing cell cancer has not been able to uncover the mystery, so scientists became a "hit-and-run mechanism" or "guerrilla mechanism" name as the synonym of carcinogenesis. Mean that the virus like guerillas, drill into cells attack target is run. What are the goals?, now some scholars believe that cancer gene. Herpes virus can make use of the flexible operation, through appropriate means activated oncogenes disappear after. If things really requires further research.

Third, the cancer gene product's function and its

The possible role in carcinogenesis

In carcinogenesis, if cancer gene's role play a leading role, in addition to cancer genes must activate this premise, the more important thing is to know about cancer gene expression product how to play. Research in cancer gene, has been focus shifted to this area. But the problems are many, and present on most issues is still in the exploration phase, also failed to form an opinion or hypothesis "embrg".

According to the product range now known, there are four categories: specific tyrosine protein kinases, membrane glycoprotein, structural protein and nucleus-binding protein. Talk about the most is the first class products. Such as Src, abl, tps and tes, and other cancer gene products are specific tyrosine protein kinases to Src products (called pp60) as an example, pp60

Can be embedded in the membrane and the substrate phosphorylation, change the sequence of amino acids in hydrophobic zone and the nature of the film, is conducive to the cells. In addition, it also makes a protein of the cytoskeleton for VN (Vinculin) phosphorylation tyrosine residues of the VN regulation microfilament collection of loss of capacity, resulting in the reticular formation Center microfilament could not form the cell deformation. Of course, the above explanation is not necessarily complete or correct, just as a way to explain it. The above interpretation of an obvious defect is no and the corresponding gene linked to the change event, namely the cancer gene products in turn trigger the tyrosine kinase to form the transformed cells cloned edge gene events, not to mention that this product is to be passed through the cell membrane and any way malignant signal is passed to the nucleus.

There is also a cancer gene products are cell membrane glycoprotein. This product is of interest because the membrane surface glycoprotein can be thought of as cells of "antenna", is to accept external information of one of the key parts of the body. "Antenna" for the number of different materials or different, different or structure of naturally accept information differently. The problem is a cancer gene manufactured "antenna" for what "normal cells in the antenna" aspects? only understood this issue could be further to the question "what kind of ' antenna ' take what information". In addition, some people want to be more precise, that cancer gene manufactured "antenna" just crude products, finally installed on the cell surface before a processing procedure, in order to get rid of something and something into the specific nature of "antenna", so understanding the process, more often than not understand "antenna" of crude process even more important.

In General, scientific invention and creativity have a certain predictability and certainty, but also many inventions is not so, the cancer gene and growth factors. In 1983, a group of researchers in the use of electronic computer to cancer gene products and other various protein for comparison, accidentally discovered the cancer gene product of sis and platelet growth factor, n-Terminal structure is extremely consistent. This is the first time found cancer gene product with a known function of protein factor, and thus as a growing points, leads to a completely new areas — cancer gene and growth factors. Growth factor is the promotion of cell division and multiplication of material, this cell transformation is one of the factors to be considered. More accidental discovery made people's horizons open Mao Leighton, aware of cancer genes by growth factors-growth factor receptors in cells of the role of information delivery approach is likely to induce cancerous cells play an important role in, as this article information delivery line not only accepts the exception information, and will interfere with or disrupt the normal flow of information and exception information from secondary and third-level or multi-level Zoom effect, so that the cell is not in accordance with the normal information directive. In accordance with such a thought, some laboratories have been found in cancer gene product is as epidermal growth factor receptor; some are through cell surface protein receptors such as Transferrin receptor, platelet growth factor receptor or insulin receptors, etc. These cancer gene product of one of the process is to increase the formation of acid-inositol, something that can be mediated several hormones, neurotransmitters and growth factor of information delivery. When inositol triphosphate system is activated, then release both as a product of the second Messenger, second-Messenger then caused a series of physiological changes. As a result of the above work for progress, the enthusiasm of people's attention, it is estimated that the momentum is there will be more people participating in this research field, in particular as a growth factor, or NGF receptor or messaging media cancer gene product, the end is the role to other cells or cells themselves receptors and delivery media direct effect or a combination of both, is somewhat appealing topics.

Although cancer gene products of the biological role of progress had been made, but problems still have a very large distance. First of all, many cancer gene products of basic properties also lack of understanding, such as those that serve as the nucleus binding protein product, essentially nothing, and the role of such products is not negligible; and secondly, because the cell is always in many enzymatic reaction system of dynamic equilibrium in this balance in any disequilibrium factor effects arising from the inevitable is a chain reaction, after a series of chain reaction after either the disequilibrium factor of elimination, reached a new balance; or do not meet the new balance so that the cell metabolism disorder occurs, leading to the ultimate become malignant. Therefore, in considering the role of the cancer gene products, it should be put in the open field of vision, efforts to find out some of these products on various metabolic processes in cells and their mutual Association. Only do this, we can carefully cancer gene products of the real situation and make a correct evaluation.

Fourth, the cancer gene expression regulation issues

Cancer gene expression of open and is a necessary cell carcinogenesis. As with other genes, cancer gene expression should be strictly controlled, once lost normal control would have serious consequences. This view is valid. The most obvious is the height of the cell cancer gene conservative. The so-called conservative means cancer genes from human evolution's earliest so far have been preserved. We all know, humans and other organisms in the evolutionary process will continue to drop negative factors, encouraging a favourable factors, the ability to become more adapted to the environment and more powerful. Cancer gene why after a long evolutionary process and enduring change? this fact alone shows they are not devoid of any merit should be useful. In this thought of enlightenment, some scholars have found certain oncogenes are really normal physiological processes play an important role in certain stages. The best example is the embryonic development and regeneration of the liver. At the foot of pregnant premature and amniotic fluid cells and placenta and placental cells, certain cancer gene expression height, which guarantee the fetal nutrition, fetal growth is necessary but has strict cell type-specific. This time, if these oncogenes in fibroblasts or other cell expression in height, the cause of osteosarcoma and fibroblasts. Here

Also raised the question: why in fetal and embryonic development related some cell types Although cancer gene expression height without cancer, while the other cell types when cancer gene expression after the height will cause cancer? answer is the former subject to the normal growth of the latter to escape the normal regulation. Liver regeneration also need some cancer gene expression, cease once the regeneration is complete, the normal expression regulation mechanism is quite sophisticated. In addition, human embryonic stage after cancer gene that is turned off, becoming de facto "silence" genes, does not show any activity, to a certain extent not be adverse factors are activated. Why is this phenomenon? this is the role of the natural regulation mechanism. This regulation we might as well be likened to the "turn off" open when you need it, when it is not required. The question is, why some adults will once again open the cancer gene switch? open switch to? open adult cancer gene and opening of the embryonic period oncogene why will produce the fundamental nature of these issues really difference? elusive, at least today. Regulation of gene expression (including cancer gene expression Regulation) of the extreme importance it has long been aware of, and in different biological species system trying to establish a control system. Gene expression regulation system is equivalent to traffic dispatching centres, through various means and ways to maintain and ensure the normal traffic without an accident. Once the scheduling command failure or disruption, the outcome would be disastrous. However, in the organism, regulation of gene expression is very difficult to study because the living cell metabolism is too complex, and involved in the regulation and control of factors certainly many, to such a complex system out of an idea and that belongs to the control system, it is not easy, especially in eukaryotic cells. It is no wonder that some researchers even think of this problem have. For cancer gene regulation issues, still know very little. First of all, need to understand cancer gene regulatory sequence in structural characteristics as well as in the different situations of change in the characteristics, on this basis, it will be possible for a specific system for regulating material basis. At the same time, not long ago, there are scholars, since normally cancer gene only very low levels of expression, even detect no expression, presumably in cell genome in a specific sequence of anti-cancer gene, which is a cancer gene (antioncogene) on regulation of gene regulation. It goes without saying that this concept has the potential of theoretical and practical significance, it consists of a sequence of traditional regulation (regulation of gene) concept, and enriched the traditional concept of meaning. In addition to the actual sense, if understood anticancer genes and cancer gene this contradictory things interdependence and constraints, that may be cancerous principle to clarify and develop cancer prevention measures. Despite the current understanding of these issues also only in a vague status, but people seem to have realized this is a meaningful and important research direction.

Five, not closing

There is no doubt that the cancer gene discovery and molecular biology of cancer research is a major event, the first because it is in molecular biology and molecular genetics developed on the basis of development and to comply with and explains some of the areas of biology basic phenomena. Therefore cancer genes as and carcinogenesis specific genes, both in theory or in practice are credible and tenable, and prove the existence of cancer gene is itself a creative results. Secondly, the causes of cancer, past the scientist had made numerous hypotheses, molecular biologists the hypothesis into cancerous principle's two great perspectives: gene mutation views and gene expression in perspective. This article introduces the concept of cancer genes have been organically unified them. Cancer genetic research to uncover the carcinogenesis principle has opened up a new way, and making it disputes the situation began to have a common Foundation, and the research direction of centralized, trend. But in this new levels, new issues have arisen, the already simplified issue and complicate, awareness seems to be experiencing a fuzzy-set — fuzzy cycle, however each loop will enable people to improve the level of awareness. Thus, by cancer genes in creation of a cancer gene-centric carcinogenesis mode is not absolutely impossible, but wish to establish such a pattern, or at least should have the following three basic condition: ① further understood cancer gene activation mechanism, in particular to clarify cancer gene expression of the structure and function and the intracellular metabolism of balance; ② at vitro and overall system established and carcinogenesis corresponds to the cancer gene expression regulation system; ③ used synthetic or genetic engineering methods of simulation of cancer genes should be can't reproduce ② results. These conditions may seem harsh, but imperative.

Of course, cannot be ruled out another possibility: cancer genes are involved in the incident just carcinogenesis of genes involved in the event of part but not all, of this possibility makes cancer genes further complicated, so when we consider a major tendencies should be made taking into account those who may be a tendency to hide, this will gradually move towards scientific truth. Just as some scientists said, looking for the true essence of carcinogenesis principle may take from a wrong move toward another error risks. Because we are an unknown quantity, to answer it, must put forward a hypothesis and theory, and once you discover these hypothesis and theory is wrong (at least not applicable), it is possible to nurture new and still be wrong hypothesis and theory. However, people will be in error in lessons, in accepted as the final resolution of the problem of cancer.