p53: Oncogene, Tumor Suppressor, or Both?
Cytogenetic  and molecular genetic  analyses have identified tumor-specific genomic changes, thus providing accumulating evidence for a genetic component in the etiology of human cancer. Cancer results from multiple genetic lesions, induced by a variety of genotoxic agents. The ensuing mutations range from point mutations via deletions in a single gene up to chromosomal rearrangements. It can be expected that some of those mutations might activate genes that stimulate cell growth, while others might inactivate genes involved in negative regulation of cell growth. Until very recently cancer biologists in their overwhelming majority have focused on activated genes, i.e. the oncogenes. This, primarily, has experimental reasons. Oncogenes are mutant alleles of proto-oncogenes. Through their mutation they have acquired novel or aberrant properties that promote cell transformation. Oncogenes function in a genetically dominant manner and provide a selective growth advantage for cells expressing them, thus facilitating their identification [3, 4]. However, one has to be aware that genomic rearrangements are frequent events for mutations causally involved in the development of cancer, and are observed in virtually all tumor cells. One would expect that such large-scale genetic alterations will, with a higher frequency, result in elimination or inactivation rather than in activation of genes. Consequently, the inactivation of negatively regulating genes should comprise an important step in the development of cancer.
KeywordsFriend Virus Tumorigenic Phenotype Abelson Murine Leukemia Promote Cell Transformation GAL4 Fusion
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