DIFFERENTIAL EFFECT OF INTERLEUKIN-4, AND TRANSFORMING GROWTH-FACTOR-BETA-1 ON EXPRESSION OF PROTOONCOGENES AND AUTOCRINE INSULIN-LIKE GROWTH-FACTOR-II IN COLORECTAL-CARCINOMA CELLS

We have compared the effect of interleukin-3 and transforming growth f actor beta 1 on proliferation and gene expression in two colorectal ca rcinoma cell lines, LS513 and LS1034. Transforming growth factor pi wa s a potent inhibitor for both cell lines and virtually abolished de no vo DNA synthesis. Interleukin-3 inhibited thymidine incorporation up t o 60 and 45%, respectively. While both cytokines exerted a comparable cytoinhibitory activity they displayed differential effects on proto-o ncogene expression. Transforming growth factor beta 1 markedly down-re gulated c-myc in LS1034 but not in LS513 cells. In contrast, expressio n of c-fos was induced by interleukin-4 in LS513 but not in LS1034 cel ls. Interestingly, in agreement with their cyto-inhibitory activity bo th cytokines suppressed the expression of insulin-like growth factor L I in LS1034, which is an autocrine growth factor for these cells. (C) 1996 Academic Press, Inc.