{"id":469747,"date":"2010-03-25T03:26:14","date_gmt":"2010-03-25T07:26:14","guid":{"rendered":"http:\/\/www.treatgene.com\/?p=543"},"modified":"2010-03-25T03:26:14","modified_gmt":"2010-03-25T07:26:14","slug":"activation-proto-oncogenes-causing-cancer","status":"publish","type":"post","link":"https:\/\/mereja.media\/index\/469747","title":{"rendered":"Activation Proto-oncogenes Causing Cancer"},"content":{"rendered":"

Oncogenes are genes that positively enhance the cell proliferation associated with cancer development<\/a>. Proto-oncogenes<\/strong> are the normal nonmutant forms of oncogenes. When the proto-oncogenes are activated, the normal cell will transform to cancerous cell<\/a>.
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\nThere are many ways of activation of proto-oncogenes<\/strong>. Activation involves a gain of function. The activation can be quantitative which involve the increase of production of an unaltered product or qualitative which involve the production of a modified product as a result of a mutation. These alterations are dominant and only affect a single allele of gene. As far as the researchers know, only RET<\/em> gene can be inherited to cause familial cancer when activated. The RET<\/em> gene involve in multiple endocrine neoplasia and familial thyroid cancer.
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Activation of Proto-oncogenes via Amplification<\/h2>\n

One of the ways of proto-oncogenes<\/strong> activation is via amplification. Many cancer cells contain multiple copies of structurally normal oncogenes. For examples, breast cancers amplify ERBB2<\/em> and sometimes MYC<\/em>. The researchers use comparative genome hybridization (CGH) technique to reveal all regions of amplification in a single experiment.
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\n\"activation<\/a><\/p>\n

Activation of Proto-oncogenes via Point Mutations<\/h2>\n

Another ways of proto-oncogenes<\/strong> activation is via point mutations. For instance, specific point mutations in ras<\/em> genes are frequently found in cells from varieties of tumours like colon, lung<\/a>, breast<\/a> and bladder cancers. The point mutations lead t amino acid substitutions and decrease the GTPase activity of the RAS protein. Consequently, the GTP-RAS signal is inactivated more slowly, leading to excessive cellular response to the signal from the receptor.
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\nAnother example of proto-oncogenes<\/strong> activation by point mutations is RET<\/em>. Mutations leading to amino acid substitutions at certain specific cysteine residues are found in multiple endocrine neoplasia type 2 and in medullary thyroid cancer.
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Activation of Proto-oncogenes by Chromosomal Translocations<\/h2>\n

The proto-oncogenes<\/strong> can be activated by chromosomal translocations too. The best known example is Philadelphia chromosome, a very small acrocentric chromosome seen in 90% of patients with chronic myeloid leukemia. It is because of a balanced reciprocal 9;22 translocation. This is an example of activation by qualitative change. The breakpoint on chromosome 9 is within an intron of the ABL<\/em> oncogene. The translocation joins most of the ABL<\/em> genomic sequence on to a gene called breakpoint cluster region (BCR<\/em>) on chromosome 22, creating a novel fusion gene. This chimeric gene is expressed to produce a tyrosine kinase related to the ABL product but with abnormal transforming properties.
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\nThere are many other rearrangements are known which produce chimeric genes. The products are transcription factors. This has been one of the most satisfying stories to emerge from cancer research<\/a>, with examples of clinical phenotypes being elegantly explained by a combination of cytogenetic<\/a> and molecular genetic findings.
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Activation of Proto-oncogenes by Transposition to an Active Chromatin Domain<\/h2>\n

On the other hand, Burkitt\u2019s lymphoma is one of the example of tumour that caused by activation of proto-oncogenes<\/strong> by transposition to an active chromatin domain. It is an example of activation by quantitative change. The oncogene was put in an environment of chromatin which is actively transcribed in antibody-producing B cells. The Burkitt\u2019s lymphoma translocations do not create novel chimeric genes. Usually, the exon of the MYC<\/em> gene is not included in the translocated material.
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\nIn conclusion, activating proto-oncogenes<\/strong> can cause cancer development. By knowing the ways of activation, maybe we can do something to prevent it via deeper cancer research.
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\n(Reference: Human Molecular Genetics from Tom Strachan and Andrew P. Read)<\/em><\/p>\n