Identification of genes involved in estrogenic action in the human prostate using microarray analysis.
Estrogens have profound effects on the developing prostate and are suspected to contribute to the development of benign prostatic hyperplasia, but the mechanism by which this hormone elicits its regulatory function still remains largely unknown. Using complementary RNA microarrays comprising approximately 10,000 oligonucleotide gene targets we compared differences in mRNA expression of estradiol-treated and untreated prostatic stromal cells in vitro. Based on a threshold of greater than twofold change, 228, 241, and 464 of the expressed genes were found to be regulated by estradiol after 10, 24, and 48 h of treatment, respectively. The secondary analysis of one estradiol-activated transcript, namely lipopolysaccharide-binding protein, and four estradiol-repressed genes, namely ras homolog gene family member E (RhoE/Rnd3), ubiquitin thiolesterase, interleukin 6, and interleukin 8 (IL-8), by real-time quantitative PCR confirmed the results of the microarray analysis. Moreover, IL-8 and RhoE were found to be down-regulated by estradiol at the protein level as well. We identified a set of genes involved in a wide range of cellular functions that are potentially important for understanding the molecular basis of estradiol action in the prostate.
Bektic
Jasmin
J
Department of Urology, University of Innsbruck, Austria.
Wrulich
Oliver A
OA
Dobler
Gabriele
G
Kofler
Kurt
K
Ueberall
Florian
F
Culig
Zoran
Z
Bartsch
Georg
G
Klocker
Helmut
H
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016000:Cluster Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D020741:rho GTP-Binding Proteins; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D004958:Estradiol; D004967:Estrogens; D020690:GTPase-Activating Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D043222:Ubiquitin Thiolesterase; D020741:rho GTP-Binding Proteins; D000099231:Lipopolysaccharide-Binding Protein; C085379:rho GTPase-activating protein; C508705:RND3 protein, human