Modulation of transforming growth factor alpha-dependent expression of epidermal growth factor receptor gene by transforming growth factor beta, triiodothyronine, and retinoic acid

✍ Scribed by J. A. Fernandez-Pol; D. J. Klos; P. D. Hamilton

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 692 KB
• Volume: 41
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240410306

✦ Synopsis

We have investigated the actions of transforming growth factor (TGF) type a on epidermal growth factor (EGF) receptor mRNA expression in MDA-468 human mammary carcinoma cells in serum-free media. We found that exposure of MDA-468 cells to TGFa results in elevated levels of EGF receptor mRNA. This increase in mRNA accumulation showed time and dose dependence. Addition of TGFj31 enhanced the accumulation of EGF receptor mRNA induced by TGFa in a time and dosedependent manner. We also found that triiodothyronine at physiological concentrations exerts synergistic control on the action of TGFa alone, or in association with TGFj31, on EGF receptor mRNA expression. Similarly, retinoic acid treatment also enhanced in a time-and dosedependent manner the TGFadependent response of EGF receptor mRNA and acted synergistically with TGFPl. The results described here suggest that optimum regulation of EGF receptor gene expression by TGFa is a complex prooess involving synergistic interactions with heterologous growth factors and hormones.

Key words oncqps, vitamin

A, thyroid hormooes, mammary cells, cancer, epithelial cells EGF has potent effects on mammalian cell growth and acts via a specific transmembrane receptor to stimulate or inhibit growth [1,2]. The EGFR transmembrane and kinase domains are homologous to the viral oncogene erb B [ 13. These observations and others [ 31 indicate that the EGF receptor can function as an oncogene. Thus, the level of EGFR gene expression must be accurately regulated in normal cells and is different in a number of transformed cells [ 11. It has been reported that EGF controls the expression of the EGFR gene in various cell types [MI. However, Abbreviations used: DME, Dult!ecm-Vogt modified Eagle's medium; EGF, epidermal growth factor; EGFR, EGF receptor; kb, kilo-RA, retinoic acid; TGF, transforming growth factor; T,, triidothyronine.