Androgen Receptor Protein Levels Are Significantly

Authors: Miriam S Butler Carmela Ricciardelli Wayne D Tilley Theresa E Hickey

Publish Date: 2013/02/27

Volume: 4, Issue: 3, Pages: 154-164

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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 glutaminerich tetratricopeptide repeatcontaining protein alpha SGTA were investigated to assess their potential role in ovarian carcinogenesis First an AR and SGTApositive 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 patientmatched stage III primary and metastatic serous ovarian tumors Ablation of SGTA protein in OVCAR3 cells significantly increased AR nuclear localization under basal p ≤ 0001 and androgenstimulated p ≤ 0001 conditions In the first clinical set AR levels were significantly lower in early I/II and latestage III/IV cancers compared with benign p ≤ 0001 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 ≤ 0001 and 0015 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 cancerThe authors thank Helen Hughes for collection of archival tissue blocks Dr Shalini Jindal for assessment of pathology and Dr Aleksandra Ochnick for TMA construction This study was supported by funds from the National Health and Medical Research Committee of Australia via a postdoctoral fellowship to TEH No 465428 and a project grant to WDT and TEH No 453628

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