title: Androgen receptor protein levels are significantly reduced in serous ovarian carcinomas compared with benign or borderline disease but are not altered by cancer stage or metastatic progression.
abstract: The androgen receptor (AR) is expressed in a majority of ovarian carcinomas, but its role in disease development remains unclear. In this study, AR and a novel AR molecular chaperone called small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) were investigated to assess their potential role in ovarian carcinogenesis. First, an AR and SGTA-positive ovarian cancer cell line was identified to examine whether SGTA influenced AR subcellular localization. Next, relative protein levels of AR and SGTA were measured in two sets of clinical samples: (1) 46 serous ovarian carcinomas (stages I-IV), 9 serous borderline tumors, and 11 benign ovarian tumors; and (2) 24 patient-matched stage III primary and metastatic serous ovarian tumors. Ablation of SGTA protein in OVCAR3 cells significantly increased AR nuclear localization under basal (p ≤ 0.001) and androgen-stimulated (p ≤ 0.001) conditions. In the first clinical set, AR levels were significantly lower in early- (I/II) and late-stage (III/IV) cancers compared with benign (p ≤ 0.001) but not borderline ovarian tumors. SGTA alone did not discriminate between groups but the AR/SGTA ratio was significantly lower in carcinomas and borderline tumors compared with benign tumors (p ≤ 0.001 and 0.015, respectively). In the second clinical set, matched primary and metastatic serous ovarian cancers did not significantly differ for any parameter measured. Collectively, our results suggest that SGTA can influence AR signaling in ovarian cancer cells and that AR signaling capacity may be reduced with the development but not metastatic progression of serous ovarian cancer.
authors: Dame Roma Mitchell Cancer Research Laboratories, School of Medicine, Faculty of Health Sciences, Level 4, Hanson Institute Building, DX NUMBER 650 801, The University of Adelaide, Adelaide, SA, 5005, Australia.
authors: Miriam S
authors: MS
authors: Butler
authors: Carmela
authors: C
authors: Ricciardelli
authors: Wayne D
authors: WD
authors: Tilley
authors: Theresa E
authors: TE
authors: Hickey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D018832:Molecular Chaperones; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C410798:AR protein, human; D002352:Carrier Proteins; D018832:Molecular Chaperones; D011944:Receptors, Androgen; C114575:SGTA protein, human