Other Free Encyclopedias » Medicine Encyclopedia » Genetics in Medicine - Part 3 » Oncogenes - Early Oncogene Research, Rna Tumor Viruses And Proto-oncogenes, Proto-oncogene Activation Without Retroviruses

Oncogenes - Proto-oncogene Activation Without Retroviruses

chromosome genetic called chromosome abl ras

The first human oncogene, called Ras, was identified in the Weinberg and Wigler experiments. The protein product of the Ras gene serves as a switch that turns growth signals on and off. Normally, the activity of this Ras switch is tightly regulated. However, single mutations (called point mutations) in critical sites of the Ras gene cause the Ras growth switch to remain constantly turned on, which contributes to cancer. Thus, some proto-oncogenes can become oncogenes by genetic point mutation. Such mutations are not dependent upon the presence of retroviruses. Instead, they can occur during normal cell division and can be caused by environmental factors such as chemicals, ultraviolet rays from the sun, and X rays. DNA repair mechanisms usually, but not always, correct such mutations.

Oncogenes also can be activated by structural changes, called "amplifications" or "translocations," that occur in the chromosomes. DNA amplification increases by several-fold a specific region of a chromosome. This can produce many copies of any genes that lie in the amplified region. If one of the genes in this region is important in driving cell growth, its over-expression due to amplification leads to uncontrolled proliferation.

In situ hybridization reveals that the product of a known oncogene, inserted into a mouse egg cell, hybridizes to multiple copies of RNA (black spots).

In the case of chromosome translocations, a proto-oncogene on one chromosome might be moved to another chromosome, resulting in the gene's structural alteration and/or aberrant expression. For example, in the translocation between chromosomes 9 and 22 that is found in CML, a protooncogene on chromosome 9, called c-Abl, is moved to chromosome 22, where it is fused to another gene called Bcr. Normally, c-Abl is a nuclear enzyme called "tyrosine kinase," which adds a phosphate molecule to proteins at an amino acid called tyrosine. Phosphorylation regulates the function of certain proteins that play important roles in stimulating cell proliferation. The fusion of Bcr and c-Abl genes creates an oncogene, called Bcr/Abl, which makes a highly overactive tyrosine kinase variant that is found in the cytoplasm instead of the nucleus. These changes in the activity and cellular location of the c-Abl proto-oncogene lead to chronic myelogenous leukemia.

Oncogenes - Short-circuiting Normal Cell Growth Mechanisms [next] [back] Oncogenes - Rna Tumor Viruses And Proto-oncogenes

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