Molecular mechanisms of oncogenesis
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- Ph.D., 1982, Calcutta University, India
One fundamental problem of cancer cells is the loss of proper regulation of cell growth. The primary research interest of our laboratory is to understand the molecular mechanism of cellular proliferation and its control. In this regard we are currently focusing on understanding the molecular biology of the human tumor suppressor p53. p53 mutation is the most frequently reported genetic defect in human cancer. Unraveling the pathway used by p53 to control cell proliferation may, therefore, lead to intervention in a large number of human cancers.
Wild-type p53 inhibits the proliferation of transformed cells, suppresses oncogene-mediated cell transformation, and eliminates the tumorigenic potential of tumor-derived cell lines. Tumor-derived mutants of p53, on the other hand, immortalize primary cells and cooperate with the ras oncogene to transform primary cells. Whereas wild-type p53 can transcriptionally activate such genes as p21, which negatively regulates cell cycle, we have demonstrated that tumor-derived p53 mutants could specifically transactivate promoters of growth-related genes such as epidermal growth factor receptor (EGFR), and this transactivation is directly related to mutant p53's capablity to induce tumorigenicity in certain cell systems. A part of our research is focused on the understanding the mechanism of mutant p53-mediated transactivation and establishing the pathway utilized by mutant p53 in enhancing tumorigenicity. For this purpose we are using recombinant DNA technology, immunological tools and cell biological approaches.
We are also working on the biological functions of p73, a homologue of p53, as well as studying the role of p53 and p73 in angiogenesis.