Expression of TGFα autocrine activity in human colon carcinoma CBS cells is autoregulated and independent of exogenous epidermal growth factor

✍ Scribed by Dianhua Jiang; Jiurong Liang; Lisa E. Humphrey; Haisu Yang; Michael G. Brattain

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 281 KB
• Volume: 175
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199805)175:2<174::aid-jcp7>3.0.co;2-l

✦ Synopsis

Autocrine transforming growth factor a (TGFa) activity and control mechanisms for its expression were examined in a representative clonal isolate (CBS4) of a well-differentiated human colon carcinoma cell line designated CBS. CBS4 cells expressed TGFa and its receptor, epidermal growth factor receptor (EGFr). Blockade of EGFr and TGFa by neutralizing antibodies inhibited clonal growth and the initiation of DNA synthesis from quiescence in CBS4 cells. Therefore, TGFa is an autocrine growth factor for CBS4 cells. Several studies have indicated that activation of the EGFr by exogenous EGF stimulates TGFa expression. However, in CBS4 cells EGF did not induce TGFa mRNA expression, indicating that EGF does not affect TGFa transcription in these cells. Exogenous treatment of exponentially growing cells with either EGF or EGFr blocking antibody enhanced release of TGFa protein into the conditioned medium. This indicated that the release of TGFa into the conditioned medium by exogenous EGF was at least partially due to the displacement of TGFa from the TGFa/EGFr complexes. Similarly to exponentially growing cells, the EGFr blocking antibody and EGF also enhanced TGFa release into the medium of CBS4 cells after release from quiescence. These results indicated that exogenous EGF had little if any effect on TGFa expression in these cells and suggested that TGFa expression might be under endogenous TGFa control. Blockade of the autocrine TGFa loop by TGFa neutralizing antibody suppressed TGFa mRNA both in exponentially growing and quiescent cells, demonstrating that autocrine TGFa is autoregulatory in this system.