In Swiss 3T3 cells, colon
tumor-promoting
deoxycholate (DOC) enhanced
DNA synthesis which was induced by
fibroblast growth factor (FGF) in the presence of
insulin. This effect was observed only when DOC was added within 10 h after the addition of FGF. DOC by itself did not induce
DNA synthesis irrespective of the presence or absence of
insulin. Similar results were obtained with other colon
tumor-promoting
bile acids such as
cholate,
chenodeoxycholate and
taurocholate. In contrast to these
bile acids, 12-O-tetradecanoylphorbol-13-acetate (TPA) induced
DNA synthesis fully without FGF in the presence of
insulin. DOC did not affect TPA-induced
DNA synthesis. Prolonged treatment of the cells with
phorbol-12,13-dibutyrate caused the down-regulation of the
phorbol ester receptor and rendered the cells unresponsive to TPA. In these cells, FGF still induced
DNA synthesis in the presence of
insulin, but the maximal level was reduced to about one third of that in the control cells. DOC did not enhance this
DNA synthesis any more. DOC did not alter the binding of FGF to the cells. These results indicate that colon
tumor-promoting
bile acids enhance the mitogenic action of FGF and thereby stimulate
DNA synthesis, although the
phorbol ester substitutes for the mitogenic action of FGF.