Transcriptional regulation of the transforming growth factor beta 1 promoter by v-src gene products is mediated through the AP-1 complex.
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.
Birchenall-Roberts
M C
MC
Division of Cancer Treatment, National Cancer Institute, Frederick Cancer Research Facility, Maryland 21701.
Ruscetti
F W
FW
Kasper
J
J
Lee
H D
HD
Friedman
R
R
Geiser
A
A
Sporn
M B
MB
Roberts
A B
AB
Kim
S J
SJ
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015291:Transforming Growth Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D015291:Transforming Growth Factors; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)