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Expression of RIZ1 protein ( Retinoblastoma‐interacting zinc‐finger protein 1 ) in prostate cancer epithelial cells changes with cancer grade progression and is modulated in vitro by DHT and E2
Author(s) -
Rossi Valentina,
Staibano Stefania,
Abbondanza Ciro,
Pasquali Daniela,
De Rosa Caterina,
Mascolo Massimo,
Bellastella Giuseppe,
Visconti Daniela,
De Bellis Annamaria,
Moncharmont Bruno,
De Rosa Gaetano,
Puca Giovanni Alfredo,
Bellastella Antonio,
Sinisi Antonio Agostino
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21920
Subject(s) - prostate cancer , cancer research , retinoblastoma , dihydrotestosterone , retinoblastoma protein , cancer , biology , immunohistochemistry , prostate , cancer cell , tamoxifen , medicine , endocrinology , cell cycle , androgen , breast cancer , hormone , biochemistry , gene
The nuclear protein methyl‐transferase Retinoblastoma‐interacting zinc‐finger protein 1 (RIZ1) is considered to be a downstream effector of estrogen action in target tissues. Silencing of RIZ1 expression is common in many tumors. We analyzed RIZ1 expression in normal and malignant prostate tissue and evaluated whether estradiol (E2) or dihydrotestosterone (DHT) treatment modulated RIZ1 in cultured prostate epithelial cells (PEC). Moreover, we studied the possible involvement of RIZ1 in estrogen action on the EPN prostate cell line, constitutively expressing both estrogen receptor (ER)‐α and β. RIZ1 protein, found in the nucleus of normal PECs by immunohistochemistry, was progressively lost in cancer tissues as the Gleason score increased and was only detected in the cytoplasmic compartment. RIZ1 transcript levels, as assayed by semi‐quantitative RT‐PCR in primary PEC cultures, were significantly reduced in cancer cells ( P < 0.05). In EPN DHT treatment significantly increased RIZ1 transcript and protein levels ( P < 0.05); E2 induced a reduction of S phase without significant changes of RIZ1 expression. In E2‐treated EPN cell extracts RIZ co‐immunoprecipitated with ERβ and ERα. Our data demonstrate that RIZ1 is expressed in normal PECs and down‐regulated in cancer cells, with a switch of its sub‐cellular localization from the nucleus to the cytoplasm upon cancer grade progression. RIZ1 expression levels in the PECs were modulated by DHT or E2 treatment in vitro. Furthermore, the E2 effects on ER‐expressing prostate cells involve RIZ1, which confirms a possible role for ER‐mediated pathways in a non‐classic E 2 ‐target tissue. J. Cell. Physiol. 221: 771–777, 2009. © 2009 Wiley‐Liss, Inc.