title: In vitro chronic administration of ERbeta selective ligands and prostate cancer cell growth: hypotheses on the selective role of 3beta-adiol in AR-positive RV1 cells.
abstract: Prostate cancer (PC) progression from androgen-dependent (AD) to castration-resistant (CR) disease is a process caused by modifications of different signal transduction pathways within tumor microenvironment. Reducing cell proliferation, estrogen receptor beta (ERbeta) is emerging as a potential target in PC chemoprevention. Among the known selective ERbeta ligands, 3beta-Adiol, the endogenous ligand in the prostate, has been proved to counteract PC progression. This study compares the effects of chronic exposure (1-12 weeks) to different ERbeta selective ligands (DPN, 8beta-VE2, 3beta-Adiol) on proliferation of human androgen-responsive CWR22Rv1 cells, representing an intermediate phenotype between the AD- and CR-PC. 3beta-Adiol (10 nM) is the sole ligand decreasing cell proliferation and increasing p21 levels. In vitro transcriptional activity assays were performed to elucidate different behavior between 3beta-Adiol and the other ligands; in these experiments the endogenous and the main ERbeta subtype activation were considered. It is concluded that ERbeta activation has positive effects also in androgen-responsive PC. The underlying mechanisms are still to be clarified and may include the interplay among different ERbeta subtypes and the specific PC microenvironment. ERbeta agonists might be useful in counteracting PC progression, although the final outcome may depend upon the molecular pattern specific to each PC lesion.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Colciago
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Ruscica
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Mornati
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Piccolella
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Montagnani-Marelli
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Ivano
authors.initials: I
authors.lastname: Eberini
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Festuccia
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Magni
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Motta
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Negri-Cesi
mesh_terms: D015113:Androstane-3,17-diol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047629:Estrogen Receptor beta; D011944:Receptors, Androgen; D015113:Androstane-3,17-diol