Evidence for c-myc in the signaling pathway for TGF-β in well-differentiated human colon carcinoma cells

✍ Scribed by Kathleen M. Mulder; Lisa E. Humphrey; Ho Gene Choi; Karla E. Childress-Fields; Michael G. Brattain

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 995 KB
• Volume: 145
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041450316

✦ Synopsis

Previously, we described a model culture system for comparing responsiveness of poorly differentiated and well-differentiated human colon carcinoma cells to exogenous growth factors. While polypeptide growth stimulators elicited an up-regulation of c-myc, as well as a mitogenic response in the well-differentiated cells, the poorly differentiated cells were insensitive to exogenous growth stimulators. We now show, by thymidine incorporation experiments and autoradiographic analysis, that transforming growth factor , (TGF-P) abrogated the insulin + transferrin (K5, = 0.8 ng/ml), as well as to nutrients (basal medium; IC,, = 0.2 ng/ml) in the well-differentiated cells. The poorly differentiated cells did not respond to TGF-p. Moreover, TGF-P (10 nglml) completely abrogated the growth factor-stimulated up-regulation of c-myc in the TGF-P responsive, welldifferentiated colon carcinoma cells. Addition of TGF-P to the TGF-P-responsive, well-differentiated cells, at a time after c-myc had been transiently up-regulated in response to growth stimulatory factors, resulted in a loss of responsiveness to TGF-6. Addition of TGF-P to these cells at increasing time periods after EIT stimulation also resulted in a loss of the TGF-p-induced repression of c-myc. The results suggest an important role for c-myc in the mechanism of action of TGF-P in well-differentiated human colon carcinoma cells.