Molecular and Cellular Endocrinology 229 (2005) 103–110 Frequent loss of estrogen and progesterone receptors in human prostatic tumors determined by quantitative real-time PCR Qing Ji a , Paul I. Liu b , Yahya Elshimali b , Andrew Stolz a,∗ a Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA b Olive View-UCLA Medical Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Sylmar, CA 91342, USA Received 1 July 2004; received in revised form 24 August 2004; accepted 25 August 2004 Abstract Relative gene expression of the estrogen receptors (ER)- (NR3A1) and ER- (NR3A2) along with progesterone receptors PR-A and PR-B (NR3C3) was determined by quantitative real-time PCR in a previously characterized panel of paired human prostate tumor and surrounding unaffected tissue (Prostate 54:275). In approximately half of these cases, a 10-fold or greater reduction in the relative mRNA levels of ER-β but not ER-α was found in the cancer as compared to normal tissue, which was also observed with unpaired samples. Immunohistochemical staining for ER- and ER- closely paralleled mRNA expression patterns for both receptors in paired samples. Reduced relative expressions of PR-B and total PR-A and PR-B isoforms were also observed in prostate tumor as compared to unaffected tissue, implying a potential role of PR in prostate tissue. The relative decrease in ER-β is greater than that observed in prior studies, suggesting that paired samples more accurately reflect differences within individual cases. These findings favor the concept that ER- mediates anti-proliferative signals and its loss in prostatic tumor promotes proliferation of these cells. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Real-time PCR; Prostatic tumor; ER- and ER- 1. Introduction Understanding of estrogen’s role in prostate gland de- velopment and tumor formation is complicated by its po- tential to directly or indirectly interact with the prostate gland (Bosland, 2000; Ho, 2004). Multiple studies have demonstrated an essential role of estrogens in prostate tu- mor formation and its potential therapeutic use in either androgen-dependent or androgen-independent prostate can- cers. In rat studies, treatment with estrogens at an early age promotes prostatic squamous hyperplasia, a pre-malignant Abbreviations: 3Adiol, 5-androstane-3,17-diol; E2, 17- estradiol; ER, estrogen receptor; ER- -/- , estrogen receptor alpha knockout (ERKO); ER- -/- , estrogen receptor beta knockout (ERKO); PR, pro- gesterone receptors ∗ Corresponding author. Tel.: +1 323 4422699; fax: +1 323 4425425. E-mail address: astolz@usc.edu (A. Stolz). lesion, and formation of prostate cancer in the Noble rat is dependent on exogenous estrogens (Cunha et al., 2001; Noble, 1977; Prins et al., 2001). In humans, a decrease in the relative ratio of androgens to estrogens and increasing estrogen levels with aging is implicated as a causative factor for benign prostatic hypertrophy (BPH) and prostate can- cer formation (Bosland, 2000; Ho, 2004). Finally, Huggins and Hodges’s observation in 1941 that estrogen treatment effectively reduced prostatic tumors and ameliorated symp- toms demonstrate their therapeutic potential (Huggins and Hodges, 1941). However, significant cardiovascular morbid- ity and thromboembolic events limit their current use (Oh, 2002). Prior to cloning of the estrogen receptors (ERs), ef- fects of estrogens were attributed to its secondary influence on the hypothalamic–pituitary–testicular axis, leading to al- terations in the serum levels of FSH and LH, and thereby indirectly regulating prostate growth (Ho, 2004; Nilsson et al., 2001). The molecular cloning of the first nuclear 0303-7207/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.mce.2004.08.012