EFFECTS OF GROWTH-FACTORS ON CELL-PROLIFERATION AND ANGIOTENSIN-II TYPE-2 RECEPTOR NUMBER AND MESSENGER-RNA IN PC12W AND R3T3 CELLS

Previous studies have suggested that the expression of angiotensin typ e 2 receptor was inversely related to cell proliferation. We examined the effects of insulin-like growth factor (ICF-1), basic fibroblast gr owth factor (bFGF), transforming growth factor beta 1 (TGF beta 1) and fetal calf serum (FCS) on cell proliferation and AT(2) binding sites and mRNA level in PC12W (rat pheochromocytoma cell line) and R3T3 (mou se fibroblast cell line) which express abundant AT(2) receptors. In bo th cell lines, serum deprivation markedly increased both AT(2) recepto r number and mRNA. However, in the absence of serum cell proliferation continued in PC12W and R3T3 at late passages (R3T3 LP) but not at ear ly passages (R3T3 EP). In PC12W, none of the three growth factors stud ied stimulated cell proliferation, but TGF beta 1 and more particularl y bFGF markedly reduced AT(2) expression. In R3T3 LP, IGF-1 and bFGF, but not TGF beta 1, slightly stimulated cell proliferation, but the th ree factors, specially bFGF, reduced AT(2) expression. In contrast, in R3T3 EP, the three growth factors significantly increased cell prolif eration, but whereas TGF beta 1 and bFGF markedly reduced AT(2) bindin g sites and mRNA, IGF-1 caused the opposite effects. These results ind icate that regulation of AT(2) expression is not correlated with cell proliferation and appears to be more complex than initially suspected. In addition, they show that the same factor can have an opposite effe ct on AT2 expression in the same cell line depending upon the cell pas sage. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.