ELSEVIER Molecular and Cellular Endocrinology 111 (1995) 75-8 1 E nrbcrinology Oestrogen-induced genes, pLIV-1 and pS2, respond divergently to other steroid hormones in MCF-7 cells Mohammed K.K. El-Tanani, Chris D. Green* Department of Biochemistry, University of Liverpool, P.O. Box 147, Liverpool, L69 3BX, UK Received 10 March 1995;accepted 3 April 1995 Abstract The level of oestrogen-responsive gene expression in breast tumours has been proposed as a predictor of the response of the tumour to endocrine (anti-oestrogen) therapy. We demonstrate that different oestrogen-responsive genes may differ in their responses to other hormones. pLIV-I and pS2 are two oestrogen-regulated genes that are expressed in the MCF-7 human breastcancercell line. We show that pLIV-I mRNA, but not pS2 mRNA, is also induced, to a lesser extent, by progesterone, .5a-dihydrotestosterone and dexamethasone. For pLIV-1, combinationsof thesehormones with oestradiol and with the pure anti-oestrogen, ICI 164384,indicate that the mechanism of its response to theseother steroid hormonesis clearly separable from its response to oestrogen.Such behaviour in breasttumours in vivo could explain the lack of absolute correlation betweenmarker geneexpression and anti-oestrogen sensitivity and betweenthe expression of individual marker genes. Keywords: Oestrogen; Progesterone; Breast cancer cell; pLIV-1; pS2. 1. Introduction Oestrogens are well established as playing a major role in the development and possibly the induction of human breast cancer (Manning et al., 1992). As a consequence, anti-oestrogenic drugs are now widely used in adjuvent therapy of breast cancer (Lerner and Jordan, 1990) and clinical trials have commenced to examine the role of the anti-oestrogen, tamoxifen, in the prevention of breast cancer (Gray, 1993). Anti-oestrogens are believed to act by competing with the hormone for binding to the oestro- gen receptor (ER) and thereby blocking the oestrogenic response of a target tissue. Between 50 and 80% of hu- man breast tumours contain detectable amounts of oestro- gen receptor (ER+ tumours), but of these only approxi- mately 50% show an objective response to anti-oestrogen therapy (McGuire et al., 1975). It is usually assumed that failure to respond results from some defect in the oestro- gen response mechanism, at a step subsequent to ligand * Corresponding author. Tel.: (0)151 794 4365; Fax: (0)151 794 We have chosen to examine the expression of two such 4349. oestrogen-induced genes, pLIV-1 and pS2, in the MCF-7, binding. This has led to attempts to distinguish responsive from unresponsive ER+ tumours on the basis of their ex- pression of an oestrogen-induced gene. The rationale be- ing that the presence of induced levels of such a gene product, in tumour cells, indicates the possession of the intact, functional oestrogen response mechanism required for anti-oestrogen sensitivity. The most commonly used oestrogen-induced gene product is a second steroid recep- tor, the progesterone receptor (Alexieva-Figusch et al., 1988). A large number of other oestrogen-regulated genes, expressed in breast cancer cells, have been identi- fied as the result of in vitro studies on oestrogen- responsive, human breast cancer cell lines (Westley and Rochefort, 1979; Bronzert et al., 1981; Masiakowski et al., 1982; Ciocca et al., 1983; Westley et al., 1984; May and Westley, 1986; Manning et al., 1988). Several have been tested for their value as predictive markers of clini- cal response to endocrine therapy (Foekens et al., 1990; Tandon et al., 1990; Manning et al., 1993). However, the use of such marker genes in this way assumes that oes- tradiol is the major, if not the sole, determinant of their level of expression. 0303-7207/95/$09.50 0 1995Elsevier ScienceIreland Ltd. All rights reserved SSDI 0303-7207(95)03550-Q