title: A role for the dehydrogenase DHRS7 (SDR34C1) in prostate cancer.
abstract: Several microarray studies of prostate cancer (PCa) samples have suggested altered expression of the "orphan" enzyme short-chain dehydrogenase/reductase DHRS7 (retSDR4, SDR34C1). However, the role of DHRS7 in PCa is largely unknown and the impact of DHRS7 modulation on cancer cell properties has not yet been studied. Here, we investigated DHRS7 expression in normal human prostate and PCa tissue samples at different tumor grade using tissue microarray and immunovisualization. Moreover, we characterized the effects of siRNA-mediated DHRS7 knockdown on the properties of three distinct human prostate cell lines. We found that DHRS7 protein expression decreases alongside tumor grade, as judged by the Gleason level, in PCa tissue samples. The siRNA-mediated knockdown of DHRS7 expression in the human PCa cell lines LNCaP, BPH1, and PC3 significantly increased cell proliferation in LNCaP cells as well as cell migration in all of the investigated cell lines. Furthermore, cell adhesion was decreased upon DHRS7 knockdown in all three cell lines. To begin to understand the mechanisms underlying the effects of DHRS7 depletion, we performed a microarray study with samples from LNCaP cells treated with DHRS7-specific siRNA. Several genes involved in cell proliferation and adhesion pathways were found to be altered in DHRS7-depleted LNCaP cells. Additionally, genes of the BRCA1/2 pathway and the epithelial to mesenchymal transition regulator E-cadherin were altered following DHRS7 knockdown. Based on these results, further research is needed to evaluate the potential role of DHRS7 as a tumor suppressor and whether its loss-of-function promotes PCa progression and metastasis.
authors: Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056, Basel, Switzerland.
authors: Julia K
authors: JK
authors: Seibert
authors: Molecular Pathology Division, Institute of Pathology, University Hospital and University of Basel, Schönbeinstrasse 40, CH-4003, Basel, Switzerland.
authors: Luca
authors: L
authors: Quagliata
authors: Molecular Pathology Division, Institute of Pathology, University Hospital and University of Basel, Schönbeinstrasse 40, CH-4003, Basel, Switzerland.
authors: Cristina
authors: C
authors: Quintavalle
authors: Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056, Basel, Switzerland.
authors: Thomas G
authors: TG
authors: Hammond
authors: Molecular Pathology Division, Institute of Pathology, University Hospital and University of Basel, Schönbeinstrasse 40, CH-4003, Basel, Switzerland.
authors: Luigi
authors: L
authors: Terracciano
authors: Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056, Basel, Switzerland.
authors: Alex
authors: A
authors: Odermatt
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D016000:Cluster Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D060787:Neoplasm Grading; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D059467:Transcriptome
chemical_list: D034741:RNA, Small Interfering; C000607165:DHRS7 protein, human; D010088:Oxidoreductases
keywords: DHRS7; SDR34C1; gene expression; proliferation; prostate cancer; tumor suppressor