Androgen Regulation of Growth Factor and Early Growth Repsonse Gene Expression in Hamster DDT1-MF2 and Human Prostate LNCAP Cells

Abstract

The Syrian hamster DDT-1 cell line was originally derived from an estrogen/androgen-induced ductus deferens tumor and has served as a model for analyzing androgen-induced growth (1). Likewise a human prostate carcinoma cell line, LNCAP, has served as a human-derived model for analyzing a stage of androgen-induced growth and may represent human prostate cancer before development of hormone autonomy (2). The mechanism of hormone-regulated growth is thought to reside in the control of PDGF-B and FGF family of growth factors, important autocrines in a wide variety of cancers. Earlier results indicate that a PDGF-B-like mRNA and acidic FGF mRNA are made by DDT-1 cells in response to androgens (3,4). In the LNCAP system, it has been demonstrated that androgens, as well as estradiol 17β, can increase aFGF mRNA levels. Therefore, the purpose of this article is to present (1) recent finding on the nature of the PDGF-B-like mRNA and gene in DDT-1 cells, (2) evidence using sense and antisense PDGF/vsis constructions that the DDT-1 vsis mRNA is important for growth of these cells, (3) data on androgen induction of the early growth response gene, Nur 77 mRNA, and (4) findings on the structure of the aFGF gene. Finally, the nature of androgen-induced early growth response gene expression and aFGF expression in LNCAP cells will be addressed, as well as the possible mechanism of why LNCAP cells are growth responsive to not only androgens, but progestins, estradiol 17β, and antiandrogens.