You have accessJournal of UrologyProstate Cancer: Basic Research VI1 Apr 20101179 ROLE OF THE TRANSCRIPTION REPRESSOR, SLUG, IN THE PATHOGENESIS OF PROSTATE CANCER Gilbert Wise, Ruben M. Pinkhasov, David Silver, James Kashanian, Theresa Jacob, Sherman Chan, and Ridwan Shabsigh Gilbert WiseGilbert Wise New York, NY More articles by this author , Ruben M. PinkhasovRuben M. Pinkhasov Brooklyn, NY More articles by this author , David SilverDavid Silver Brooklyn, NY More articles by this author , James KashanianJames Kashanian Brooklyn, NY More articles by this author , Theresa JacobTheresa Jacob Brooklyn, NY More articles by this author , Sherman ChanSherman Chan Brooklyn, NY More articles by this author , and Ridwan ShabsighRidwan Shabsigh Brooklyn, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.680AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES During tumor progression, several key molecular players are involved that allow cells to leave their surroundings and migrate to a distant site. Loss of the cell adhesion factor, E-cadherin and up regulation of Slug, (a transcription repressor involved in epithelial to mesenchymal transition) has been shown to be associated with poor tumor prognosis. Our study investigated Slug and its relation to E-cadherin expression to elucidate its role in pathogenesis of prostate cancer (CaP). We hypothesize that over expression of Slug down regulates cell adhesion factor (E-cadherin) while resulting in cell de-differentiation and migration in CaP cells. METHODS Prostate tissue was obtained from a random selection of core biopsy specimens of men undergoing assessment for neoplasia or post radical prostatectomy specimens (n=65). Slug and E-cadherin mRNA transcripts were determined by real-time RT-PCR. Principal risk factors, PSA levels, Gleason scores, and tumor stage, were also compared. RESULTS All tissues with documented CaP (n=35; 54%) and prostate intraepithelial neoplasia (n=2; 3%) demonstrated increased expression of Slug with repression of E-cadherin. There was a significantly higher amount of Slug transcripts in CaP tissues as compared to that in benign tissues (6-fold vs 2-fold, respectively of internal control; p<0.05). A statistically significant association was found between Slug up regulation and E-cadherin down regulation (r=0.79). Transcripts of Slug were about 7 times that of E-cadherin in CaP samples, while they were less than 1.2 times that of E-cadherin in tumor negative tissues (p=0.01). The Slug/E-cadherin ratio is significantly higher in CaP tissues than that in benign samples. CONCLUSIONS Slug up regulation and associated E-cadherin down regulation were observed in CaP biopsy tissues. This is the first study that provides evidence of Slug/E-cadherin relationship in prostate cancer. Our results concur with the accumulating reports on the role of Slug in tumor invasion. Further elaboration of its expression in the genetic architecture of the prostate and the molecular repercussions therein, could possibly identify causative/susceptibility mechanisms and new therapeutic targets. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e457 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gilbert Wise New York, NY More articles by this author Ruben M. Pinkhasov Brooklyn, NY More articles by this author David Silver Brooklyn, NY More articles by this author James Kashanian Brooklyn, NY More articles by this author Theresa Jacob Brooklyn, NY More articles by this author Sherman Chan Brooklyn, NY More articles by this author Ridwan Shabsigh Brooklyn, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prostate cancer is the most common gender-specific malignancy in men in the USA. Androgen-deprivation therapy (ADT) is commonly used in the treatment of metastatic or recurrent prostate cancer. The use of ADT is increasing with the advocacy of adjuvant and neoadjuvant ADT for treating asymptomatic patients with locally advanced prostate cancer. Although the use of ADT has resulted in improved survival in men with advanced prostate cancer, ADT, with its resulting severe hypogonadism, causes profound metabolic side-effects. We comprehensively reviewed previous reports using Medline searches of English-language literature (1950 to the present), with the keywords 'hypogonadism', 'testosterone', 'androgen deprivation therapy', 'hormonal treatment', 'prostate cancer', 'diabetes', 'metabolic syndrome', and 'cardiovascular disease'. Men with prostate cancer who undergo long-term ADT are at greater risk of developing dyslipidaemia, insulin resistance, hyperglycaemia and metabolic syndrome. These metabolic and physiological changes are a direct result of the induced severe hypogonadism and might predispose patients to a greater risk of cardiovascular morbidity and mortality. There is a need for prospective studies aimed and designed to investigate the metabolic and cardiovascular adverse effects of ADT, and assess the benefit/risk ratio, especially in special populations such as diabetics.