ONCOGENE TRANSFORMATION OF PC CL3 CLONAL THYROID-CELL LINE INDUCES ANAUTONOMOUS PATTERN OF PROLIFERATION THAT CORRELATES WITH A LOSS OF BASAL AND STIMULATED PHOSPHOTYROSINE PHOSPHATASE-ACTIVITY

The effects of the stable expression of E1A and/or middle T oncogenes on the proliferative activity of PC Cl3 normal thyroid cells are repor ted. The proliferation of PC Cl3 cells is mainly regulated by insulin and TSH in a stimulatory way and by somatostatin in an inhibitory fash ion. The transformed cell lines, named PC Py and PC E1A Py, show an au tonomous pattern of proliferation. The blockade of phosphotyrosine pho sphatase activity with vanadate increased the proliferation rate of PC Cl3 under basal and stimulated conditions and completely prevented th e inhibitory activity of somatostatin, suggesting that in PC Cl3 cells , a tonic tyrosine phosphatase activity regulates basal and stimulated proliferation, and that a somatostatin-dependent increase in this act ivity may represent a cytostatic signal. Conversely, in both PC Py and PC E1A Py, vanadate did not modify basal and stimulated proliferation . We analyzed tyrosine phosphatase activity in the different cell line s basally and under conditions leading to the arrest of cell prolifera tion: confluence (contact inhibition), growth factor deprivation (star vation), and somatostatin treatment. Under basal conditions, tyrosine phosphatase activity was significantly lower in PC Py and PC E1APy cel l lines than that in the normal cells. The inhibition of the prolifera tion induced by contact inhibition or somatostatin treatment was accom panied by an increase in tyrosine phosphatase activity only in PC Cl3 cells. The reduction in tyrosine phosphatase activity in PC E1APy cell s correlated with a significant reduction in the expression of R-PTP e ta, a tyrosine phosphatase cloned from PC Cl3 cells. Conversely, the e xpression of another receptor-like PTP, PTP mu, was unchanged. Thus, P TP eta may be a candidate to mediate inhibitory signals (i.e. activati on of somatostatin receptors or cell to cell contact) on the prolifera tive activity of PC Cl3 cells, and the reduction of its expression in the transformed cell lines may lead to an alteration in the control of cell proliferation.