Takeyama Y, Kaibuchi K, Ohyanagi H, Saitoh Y, Takai Y
FEBS Lett. 1985 Dec 2;193(2):153-8. doi: 10.1016/0014-5793(85)80141-1.
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.
在瑞士3T3细胞中，结肠肿瘤促进剂脱氧胆酸盐（DOC）可增强由成纤维细胞生长因子（FGF）在胰岛素存在下诱导的DNA合成。仅当在添加FGF后10小时内添加DOC时才观察到这种效应。无论有无胰岛素，DOC自身均不诱导DNA合成。用其他结肠肿瘤促进胆汁酸如胆酸盐、鹅去氧胆酸盐和牛磺胆酸盐也得到了类似结果。与这些胆汁酸相反，12-O-十四烷酰佛波醇-13-乙酸酯（TPA）在胰岛素存在下无需FGF即可完全诱导DNA合成。DOC不影响TPA诱导的DNA合成。用佛波醇-12,13-二丁酸酯对细胞进行长时间处理会导致佛波醇酯受体下调，并使细胞对TPA无反应。在这些细胞中，FGF在胰岛素存在下仍可诱导DNA合成，但最大水平降至对照细胞的约三分之一。DOC不再增强这种DNA合成。DOC不改变FGF与细胞的结合。这些结果表明，结肠肿瘤促进胆汁酸增强FGF的促有丝分裂作用，从而刺激DNA合成，尽管佛波醇酯可替代FGF的促有丝分裂作用。
