Transcriptional regulation of the transforming growth factor beta 1 promoter by v-src gene products is mediated through the AP-1 complex.

Abstract

Growth factor-independent 32D-src and 32D-abl cell lines, established by infecting the interleukin-3-dependent myeloid precursor cell line (32D-123) with retroviruses containing the src or abl oncogene, were used to study transcriptional regulation of transforming growth factor beta 1 (TGF-beta 1) mRNA. Analysis of different TGF-beta 1 promoter constructs regulated by pp60v-src indicated that sequences responsive to high levels of src induction contain binding sites for AP-1. Both src and serum induced expression of the c-fos and c-jun genes in myeloid cells, resulting in transcriptional activation of the TGF-beta 1 gene. We found that serum treatment increased TGF-beta 1 mRNA levels in 32D-123 cells and that the v-Src protein could replace the serum requirement by stimulating binding to the AP-1 complex of the TGF-beta 1 promoter, thereby mediating the induction of TGF-beta 1 transcription.