GROWTH REQUIREMENTS AND ONCOGENE EXPRESSION IN THE HUMAN THYROID-CELLLINE SGHTL-34

The SV40 T-antigen-transfected human thyroid cell line SGHTL-34 was us ed to investigate the effect of thyrotropin (TSH), insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) on c-fos and c-erb B/EGF receptor (EGF-R) mRNA expression and their role in human thyroid cell proliferation. EGF caused a transient 8- and 4-fold increase in c-fos mRNA level after 30 min in serum/hormone-deprived and in logarit hmically growing cells, respectively. EGF was only mitogenic in the pr esence of serum, as measured by H-3-thymidine incorporation and cell c ounting. TSH had no detectable effect on c-fos mRNA expression and no mitogenic effect on the SGHTL-34 cells. IGF-1 showed no effect alone o r in combination with EGF or TSH on either proliferation or c-fos mRNA expression. Our data suggest that increased c-fos mRNA levels are par t of the mitogenic pathway, but are insufficient to engender a mitogen ic response. SGHTL-34 cells produced high levels of transforming growt h factor-alpha (TGF-alpha) and c-erbB/EGF-R mRNA, also seen in thyroid papillary carcinomas. The TGF-alpha protein was detected in condition ed medium from the SGHTL-34 cells, indicating that TGF-alpha may funct ion as an autocrine growth factor. Our data show that the c-erbB/EGF-R mRNA level is regulated by growth factors and hormones in the SGHTL-3 4 cell line. The SGHTL-34 cells may therefore represent a useful model system for studying the role of TGF-alpha and EGF-R in thyroid carcin ogenesis.