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We are interested in understanding the mechanism(s) of signaling by transforming growth factor beta (TGF-ß) in normal and cancer cells. TGF-ß is a multi-functional cytokine responsible for regulating growth and differentiation of a wide variety of cell types and tissues. It is a potent inhibitor of normal epithelial cell proliferation and posses tumor suppressing activity.  The majority of human tumors are of epithielial origin and their proliferation is no longer inhibited by TGF-ß. This usually arises either from a loss of key signaling molecules in the TGF-ß signal transduction pathway, e.g. TGF-ß receptors, or from activation of oncogenes. TGF-ß can postively regulate expression of many tumor suppressor genes which cause the cell to stop proliferation and yet negatively regulate expression of many protooncogenes/oncogenes which promote cell cycle progression. The action of TGF-ß in normal epithelial cells is to downshift the engine that drives cell proliferation by shifting the balance of the activity of the oncogene and tumor suppressor gene. More...

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