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LINK BETWEEN p16INK4a AND CANCER
A recent study published in March 1996 issue of Cell describes the knockout of p16INK4a. This study shows that the knockout of the gene is associated with spontaneous development of tumors in mice before they reach 34 weeks of age. In addition, these mice were more susceptible than the wild-type mouse to carcinogens and when exposed to UV irradiation and 9,10 dimethyl-1,2-benzanthracene developed malignant tumors at an average age of 9 weeks. Although these results confirm the prior findings that p16INK4a may in fact be involved in tumor suppression, the kncokouts also lacked a second gene, p19ARF (alternative reading frame) that may also play a role in cell cycle progression. However, mutation in p19ARF alone can not lead to tumorigenesis. These findings give credence to the idea that p16 may be a true suppressor gene. REFERENCES
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Two genes, p16 (also known as CDKN2, INK4a or MTS1) and p15 (also known as INK4B, or MTS2) which map to the on chromosome 9p21, encode proteins that function as negative regulators of cell cycle. Therefore, they are thought to represent suppressor genes. The encoded proteins inactivate the specific cyclin-protein kinase complexes such as the D-type-cyclin dependent kinases, cdk4 and cdk6 that are involved in progression of the cell cycle. Deletion of p16 and p15 is frequently observed in cancer cell lines and some malignant tumors such as acute lymphoblastic leukemia of chilhood, melanomas, gliomas, as well as carcinoma of the pancreas, esophagus, lung, bladder, head, and neck. The murine p16INK4a and p15INK4b have recently been cloned and both genes map to position C3-C6 on mouse chromosome 4, in a region syntenic with human chromosome 9p. p16INK4a has a limited expression in normal mouse tissues, whereas, p15INK4b shows a ubiquitous expression.
