The Physiology Of Transforming Growth Factor-α

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This chapter discusses the role of transforming growth factor- α (TGF- α) in the proliferation of the normal cells and its potential importance in tumor development. Research during the past few years had made it evident that TGF- α plays a role in the physiology of the normal cells and tissues. All types of normal epithelial cells synthesize TGF- α. These cells have TGF- α receptors, thus making them responsive to the action of TGF- α in an autocrine fashion. Even though there no direct proof in vivo, it is likely that a normal role of the endogenous TGF- α synthesis in these epithelia is to drive their proliferation. The effect of TGF- α on substrate-dependent colony formation of human keratinocytes has been studied in detail. TGF- α is a normal physiological ligand of the TGF- α receptor that plays a role in cellular proliferation not only in the adult, but presumably even more importantly in organ and tissue development. Its role in normal tissues certainly does not exclude a role in the establishment and maintenance of the malignant character of the tumor cells. TGF- α plays a role in and contribute to phenotypic transformation and stimulates the proliferation of the tumor cells and of the tumor in vivo. TGF- α expression influences the invasive behavior of the tumor cells and contributes to the induction of neovascularization of the tumors and to the malignancy-induced hypercalcemia.

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