Cancer proto-oncogenes

Several inherited cancer syndromes are also known to result from mutations in proto-oncogenes. An example is given by the RET proto-oncogene. Depending on the type of mutation and on which part of the gene is affected, RET mutations can lead to multiple endocrine neoplasia 2A or 2B or familial medullary thyroid carcinoma. These familial cancers are inherited in autosomal dominant fashion. A second example is the CDK4 proto-oncogene, which when mutated can cause familial melanoma. 

Unlike tumor suppressors, in which loss-of-function mutations are required in both copies of the gene in a specific cell, a single gain-of-function mutation in a proto-oncogene is usually sufficient to give rise to cancer. 

Although the study of inherited cancer syndromes has led to the identification of a number of tumor suppressor genes and oncogenes, the inherited cancer syndromes are thought to account for only about 1% of all cancers. However, somatic (as opposed to germline) mutations in many of these tumor suppressors and proto-oncogenes play a key role in the causation of noninher-... 

Each cell of the human body carries the potential to become cancerous in the form of its proto-oncogenes. The case of the src gene is far from unique. A great many proto-oncogenes have been discovered some of the best known are myc, myb, ras, fes, fins, fos, and jun (these names derive from the retrovirus in which they were discovered e.g., ras comes from a rat sarcoma virus and fes from a feline sarcoma virus). It follows that each of our cells harbors a number of protooncogenes, each of which may become activated and contribute to the formation of a tumor. 

The plot seemed to be getting much simpler. All vertebrate cells seemed to carry a common set of proto-oncogenes. These genes could become converted into potent cancer-causing genes either by retroviruses or by nonviral mutagens. Proto-oncogenes seemed to represent the ultimate root causes of cancer. 

So far, our story has focused on mutated single proto-oncogenes—for example src or ras—as key entities in the generation of cancer. A little reflection will convince us that the story cannot be that simple. 

By now, we have put together a lot of the cancer story. We know that cancer is a disease originating in a single cell that has overcome the normal limits to its growth and proliferation and that mutations in proto-oncogenes and/or tumor suppressor genes are required for this to happen. Beyond that, we know that multiple such mutations are usually required. 

Remarkably, viral oncogene relatives are present in normal cells—these are termed proto-oncogenes. Therefore, each cell in the human body carries the potential to become cancerous in the form of its proto-oncogenes, which include myc, ms, myb, fes, fms, fos, and jun. 

The sequence of events from mutations or damage to proto-oncogenes and leads to tumour suppressor genes, loss of development of cancer, with its metabolic disturbances and cachexia. Finally these changes can lead to... 

Ras, a historical proto-oncogene, is frequently mutated in many human cancers, including 90% of pancreatic cancers, 50% of colorectal cancers, 30% of lung cancers, and 15-30% of melanomas [10-12]. There are three Ras genes that encode four family members K-Ras (two alternatively spliced isoforms), H-Ras, and N-Ras. Mutations are most commonly found in K-Ras [13]. These mutations result in impaired GTP hydrolysis, which shifts the equilibrium toward GTP-bound active Ras, and results in constitutive intracellular signaling. 

The accumulation of cancer cells is the net effect of cell proliferation and apoptosis (T4). The inhibition of apoptosis by activation of the proto-oncogene... 

Since point mutations of the ras proto-oncogene are often found in cancer, a vaccine was made with mutated ras peptides mixed with Detox. In a phase I study, CD4+ proliferation and CD8+ cytotoxicity specific to the mutated peptide, were observed. The side effects were minimal and one patient showed a stabilisation of the disease [213],... 

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