Effects of growth factors on cell proliferation and angiotensin II type 2 receptor number and mRNA in PC12W and R3T3 cells.

Previous studies have suggested that the expression of angiotensin type 2 receptor was inversely related to cell proliferation. We examined the effects of insulin-like growth factor (IGF-1), basic fibroblast growth factor (bFGF), transforming growth factor beta1 (TGFbeta1) and fetal calf serum (FCS) on cell proliferation and AT2 binding sites and mRNA level in PC12W (rat pheochromocytoma cell line) and R3T3 (mouse fibroblast cell line) which express abundant AT2 receptors. In both cell lines, serum deprivation markedly increased both AT2 receptor number and mRNA. However, in the absence of serum cell proliferation continued in PC12W and R3T3 at late passages (R3T3 LP) but not at early passages (R3T3 EP). In PC12W, none of the three growth factors studied stimulated cell proliferation, but TGFbeta1 and more particularly bFGF markedly reduced AT2 expression. In R3T3 LP, IGF-1 and bFGF, but not TGFbeta1, slightly stimulated cell proliferation, but the three factors, specially bFGF, reduced AT2 expression. In contrast, in R3T3 EP, the three growth factors significantly increased cell proliferation, but whereas TGFbeta1 and bFGF markedly reduced AT2 binding sites and mRNA, IGF-1 caused the opposite effects. These results indicate that regulation of AT2 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 effect on AT2 expression in the same cell line depending upon the cell passage.