癌基因[编辑]
癌基因（英语：Oncogene，亦称为致癌基因）是细胞遗传物质的一部分, 它们参与细胞从正常生长状态到肿瘤的过程。它们通过诱导或突变被激活。
原癌基因[编辑]
原癌基因(proto-oncogene)是参与细胞生长、细胞分裂和细胞分化的正常基因。但当其发生突变后，例如基因序列被改变，就会变成致癌基因。也就是说，原癌基因是致癌基因的前体。它们会在诸如放射性物质，化学物质和病毒的作用影响下过渡成引发癌症的形式。截至2004年，已经发现超过100种的原癌基因。
原癌基因根据其编码的蛋白质被分类：
很多影响细胞生长的因子都可被视为原癌基因。如果这些基因发生突变，通常只会使编码的蛋白质丧失原有功能，细胞分裂停止，进而引发程序性细胞死亡（细胞凋亡）。这并不会对机体产生影响，因为附近有分裂能力的正常细胞可以通过有丝分裂替代凋亡的细胞。
但突变也可能会产生致癌基因并推动细胞分裂，甚至不受控制。这样，致癌基因就会导致癌症的形成。
Oncogene
An oncogene is a gene that has the potential to cause cancer.[1] Intumor cells, they are often mutated or expressed at high levels.[2]
Most normal cells undergo a programmed form of death (apoptosis). Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead.[3] Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer. Many cancer drugs target the proteins encoded by oncogenes.[2][4][5][6]
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Classification[edit]
There are several systems for classifying oncogenes,[16][17] but there is not yet a widely accepted standard. They are sometimes grouped both spatially (moving from outside the cell inwards) and chronologically (parallelling the "normal" process of signal transduction). There are several categories that are commonly used:
| Category | Examples | Cancers | Gene functions |
| Growth factors, or mitogens | c-Sis | glioblastomas, fibrosarcomas,osteosarcomas, breast carcinomas, and melanomas[18] | induces cell proliferation. |
| Receptor tyrosine kinases | epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), andvascular endothelial growth factor receptor (VEGFR),HER2/neu | Breast cancer, gastrointestinal stromal tumours, non-small-cell lung cancer and pancreatic cancer[19] | transduce signals for cell growth and differentiation. |
| Cytoplasmictyrosine kinases | Src-family, Syk-ZAP-70family, and BTK family of tyrosine kinases, the Abl gene in CML - Philadelphia chromosome | colorectal and breast cancers, melanomas, ovarian cancers, gastric cancers, head and neck cancers, pancreatice cancer, lung cancer, brain cancers, and blood cancers[20] | mediate the responses to, and the activation receptors of cell proliferation, migration, differentiation, and survival [21] |
| CytoplasmicSerine/threonine kinases and their regulatory subunits | Raf kinase, and cyclin-dependent kinases (throughoverexpression). | malignant melanoma, papillary thyroid cancer, colorectal cancer, and ovarian cancer[22] | Involved in organism development, cell cycle regulation, cell proliferation, differentiation, cells survival, and apoptosis [23] |
| Regulatory GTPases | Ras protein | adenocarcinomas of the pancreas and colon, thyroid tumors, and myeloid leukemia[24] | involved in signalling a major pathway leading to cell proliferation.[25] |
| Transcription factors | myc gene | malignant T-cell lymphomas and acute myleoid leukemias, breast cancer, pancreatic cancer, retinoblastoma, and small cell lung cancer [26] | -They regulate transcription of genes that induce cell proliferation. |
More detailed information for the above Table:
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- Growth factors are usually secreted by either specialized or not specialized cells to induce cell proliferation in themselves, nearby cells, or distant cells. An oncogene may cause a cell to secrete growth factors even though it does not normally do so. It will thereby induce its own uncontrolled proliferation (autocrine loop), and proliferation of neighboring cells. It may also cause production of growth hormones in other parts of the body.
- Receptor Tyrosine Kinases add phosphate groups to other proteins to turn them on or off. Receptor kinases add phosphate groups to receptor proteins at the surface of the cell (which receive protein signals from outside the cell and transmit them to the inside of the cell). Tyrosine kinases add phosphate groups to the amino acid tyrosine in the target protein. They can cause cancer by turning the receptor permanently on (constitutively), even without signals from outside the cell.
- Ras is a small GTPase that hydrolyses GTP into GDP and phosphate. Ras is activated by growth factor signaling (i.e., EGF, TGFbeta) and acting like a binary switch (on/off) in growth signaling pathways. Downstream effectors of Ras include three mitogen-activated protein kinases Raf a MAP Kinase Kinase Kinase (MAPKKK), MEK a MAP Kinase Kinase (MAPKK), and ERK a MAP Kinase(MAPK), which in turn regulate genes that mediate cell proliferation.
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