LOSS OF THYROTROPIN REGULATION AND TRANSFORMING GROWTH FACTOR-BETA-INDUCED GROWTH ARREST IN ERBB-2 OVEREXPRESSING RAT-THYROID CELLS

Amplification of erbB-2 gene and overexpression of gp185erbB-2 gene pr oduct is found in approximately one-third of primary human breast and ovarian cancer. Overexpression of gp185erbB-2 was recently found in hu man papillary thyroid carcinomas, but not in thyroid follicular carcin omas or adenomas. The erbB-2 gene encodes a cell surface growth factor receptor with intrinsic tyrosine kinase activity. Wild type human erb B-2 has been shown to act as a potent oncogene when overexpressed in m ouse fibroblasts. To test whether overexpression of normal human erbB- 2 gene can transform epithelial differentiated rat thyroid cells, thes e cells were infected with a recombinant retroviral expression vector containing the erbB-2 protooncogene. Rat thyroid cells expressing high levels of gp185erbB-2 do not display a fully transformed and tumorige nic phenotype. However, the isolated cell clones that overexpress gp18 5erbB-2, show changes in their growth properties if compared to normal thyroid cells, since they can grow in absence of thyrotropin, the mai n growth factor controlling thyroid cell proliferation in vitro, and d o not respond to the growth inhibitory effect of transforming growth f actorbeta.