EXCESSIVE ACTIVATION OF TYROSINE KINASES LEADS TO INHIBITION OF PROLIFERATION IN A THYROID-CARCINOMA CELL-LINE

Autocrine stimulation of growth is a hallmark of many tumor cell lines . In this work we investigated the synthesis and secretion of growth f actors and the expression of their corresponding receptors in HTC-TSHr thyroid carcinoma cells. These cells synthesize epidermal growth fact or (EGF) receptors and platelet-derived growth factor beta (PDGF beta) receptors and in addition transforming growth factor alpha (TGF alpha ), PDGF-A and PDGF-B chains, respectively Addition of EGF or PDGF-BB t o the culture medium resulted in growth inhibition of HTC-TSHr cells. In contrast, treatment of the cells with low concentrations of neutral izing anti-TGF alpha antibodies or tyrosine kinase inhibitors led to s timulation of cell proliferation. Low concentrations of neutralizing a nti-PDGF-B antibodies did not affect growth of the cells. As expected, cell proliferation was inhibited when high concentrations of either n eutralizing anti-TGF alpha antibodies or anti-PDGF-B antibodies were a pplied. PDGF-AA did not influence growth of HTC-TSHr cells. We conclud e that growth of HTC-TSHr thyroid carcinoma cells is influenced by two autocrine loops between TGF alpha and EGF receptors and between PDGF- B and PDGF beta receptors. However, our data suggest that excessive ac tivation of tyrosine kinase receptors in these cells results in a rela tive inhibition rather than stimulation of growth.