TY - JOUR
T1 - Enhancement of growth factor-induced DNA synthesis by colon tumor-promoting bile acids in Swiss 3T3 cells. Their different mode of action from that of phorbol esters
AU - Takeyama, Yoshifumi
AU - Kaibuchi, Kozo
AU - Ohyanagi, Harumasa
AU - Saitoh, Yoichi
AU - Takai, Yoshimi
N1 - Funding Information:
The authors are grateful to Miss Junko Yamaguchi for her skillfui secretariala ssistance. This investigation was supported in part by researchg rantsf rom the Scientific ResearchF und of the Ministry of Education,S ciencea nd Culture, Japan (1984, 1985),t he Yamanouchi Foundation for Researcho n Metabolic Disorders (1984)a nd Research Foundation for Cancer and Car-diovascularD iseases( 1985).
PY - 1985/12/2
Y1 - 1985/12/2
N2 - 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.
AB - 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.
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U2 - 10.1016/0014-5793(85)80141-1
DO - 10.1016/0014-5793(85)80141-1
M3 - Article
C2 - 3905436
AN - SCOPUS:0022337095
SN - 0014-5793
VL - 193
SP - 153
EP - 158
JO - FEBS Letters
JF - FEBS Letters
IS - 2
ER -