title: Effects of dutasteride on the expression of genes related to androgen metabolism and related pathway in human prostate cancer cell lines.
abstract: Androgens play an important role in controlling the growth of the normal prostate gland and in the pathogenesis of benign prostate hyperplasia, and prostate cancer. Although testosterone is the main androgen secreted from the testes, dihydrotestosterone (DHT), a more potent androgen converted from testosterone by 5alpha-reductase isozymes, type I and II, is the major androgen in the prostate cells. The aim of this study is to investigate the cellular and molecular effects of dutasteride, a potent inhibitor of 5alpha-reductase type I and type II, in androgen-responsive (LNCaP) and androgen-unresponsive (DU145) human prostate cancer(PCa) cell lines. The expression pattern of 190 genes, selected on the basis of their proved or potential role in prostate cancerogenesis related to androgen signalling, were analysed using a low density home-made oligoarray (AndroChip 2). Our results show that dutasteride reduces cell viability and cell proliferation in both cell lines tested. AndroChip 2 gene signature identified in LNCaP a total of 11 genes differentially expressed (FC >or= +/-1.5). Eight of these genes, were overexpressed and three were underexpressed. Overexpressed genes included genes encoding for proteins involved in biosynthesis and metabolism of androgen (HSD17B1;HSD17B3;CYP11B2), androgen receptor and androgen receptor co-regulators (AR;CCND1), and signal transduction(ERBB2; V-CAM; SOS1) whereas, underexpressed genes (KLK3; KLK2; DHCR24) were androgen-regulated genes (ARGs). No differentially expressed genes were scored in DU145. Microarray data were confirmed by quantitative real-time PCR assay (QRT-PCR). These data offer a selective genomic signature for dutasteride treatment in prostate epithelial cells and provide important insights in prostate cancer pathophysiology.
authors.affiliation: Department of Biopathology and Diagnostic Imaging, Tor Vergata University, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Biancolella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Valentini
authors.forename: Daniela
authors.initials: D
authors.lastname: Minella
authors.forename: Lucia
authors.initials: L
authors.lastname: Vecchione
authors.forename: Franca
authors.initials: F
authors.lastname: D'Amico
authors.forename: Giovanni
authors.initials: G
authors.lastname: Chillemi
authors.forename: Paolo
authors.initials: P
authors.lastname: Gravina
authors.forename: Susana
authors.initials: S
authors.lastname: Bueno
authors.forename: Gianluca
authors.initials: G
authors.lastname: Prosperini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Desideri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000728:Androgens / Q000378:metabolism*; D001378:Azasteroids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000068538:Dutasteride; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism
chemical_list: D058891:5-alpha Reductase Inhibitors; D000728:Androgens; D001378:Azasteroids; D000068538:Dutasteride