Regulation of a promoter of the fibroblast growth factor 1 gene in prostate and breast cancer cells.
FGF-1 mRNA is expressed in the prostate cancer cell lines LNCaP and PC-3 and in the breast carcinoma cell line MDA-MB-231. Levels of FGF-1 mRNA have been shown to be up-regulated by serum, phorbol esters, and combinations of growth factors. It was shown that the major FGF-1 mRNA species expressed following serum stimulation in MDA-MB-231 cells is FGF-1.C. To better understand the potential role of FGF-1 in human prostate and breast cancer, we began an analysis of the cis- and trans-acting elements of one of its promoters required for the serum, PMA, and androgen regulation in breast and prostate cancer cell lines. We show that FGF-1.C steady-state mRNA levels are increased following serum or PMA stimulation of PC-3 cells. Further, we determine the FGF-1.C transcription start site in PC-3 cells. By sequence analysis, we show that consensus AP1, AP2, and Sp1 sites and ARE- and CRE-near consensus elements are present in the immediate 5' region of the FGF-1.C transcription start site. Gel-shift assays show that oligonucleotides containing FGF-1.C AP1, AP2, or Spl sequences form specific DNA-protein complexes with nuclear extracts from PC-3 cells. To determine if these or other cis-acting sequences are responsible for the serum, androgen, or growth factor regulation of FGF-1 expression, fragments of the FGF-1.C promoter region were cloned upstream of the luciferase reporter gene. We show that FGF-1 synergizes with androgen to enhance FGF-1.C transcription in LNCaP cells. We further show that the DNA fragment containing sequence up to 1614 nucleotides upstream of the FGF-1.C transcription start site is sufficient for stimulating promoter activity following serum treatment of MDA-MB-231 cells. Thus, FGF-1.C promoter contains sequences that are important for androgen or serum stimulation in prostate and breast cancer cells.
Payson
R A
RA
Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus 43210, USA.
Chotani
M A
MA
Chiu
I M
IM
D000728:Androgens / Q000494:pharmacology; D001483:Base Sequence; D001769:Blood; D001943:Breast Neoplasms / Q000235:genetics*; D002460:Cell Line; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000737:chemistry; D016220:Fibroblast Growth Factor 1 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017421:Sequence Analysis; D013755:Tetradecanoylphorbol Acetate; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000728:Androgens; D018076:DNA, Complementary; D012333:RNA, Messenger; D016220:Fibroblast Growth Factor 1; D013755:Tetradecanoylphorbol Acetate