Regulation of a promoter of the fibroblast growth factor 1 gene in prostate and breast cancer cells

被引:24
作者
Payson, RA
Chotani, MA
Chiu, IM [1 ]
机构
[1] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA
[2] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0960-0760(98)00051-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 PIMA 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 Sp1 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. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:93 / 103
页数:11
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