Abstract 3559: FKBP5 is an androgen-responsive gene in thyroid cancer cells.

Abstract

Abstract There has been a steady increase in the incidence thyroid cancer in the United States, with over 56,000 cases predicted for 2012. The increased aggressiveness of the disease and poorer clinical outcome in men and postmenopausal women may be due to androgen/androgen receptor (AR) related functions. FK506 binding protein 51 (FKBP5) is a member of the immunophilin family and plays a role in steroid receptor function. Further, FKBP5 regulates the NFkB and AKT pathways and is thought to be relevant to the neoplastic process. Immunohistochemical analysis of 38 papillary thyroid cancer (PTC) specimens indicated that androgen receptor is expressed in both normal and cancerous epithelial cells, in both men and women. Analysis of AR expression in thyroid cell lines indicated that the normal thyroid cell line, Nthy-ori 3-1 and PTC cell lines BCPAP and TPC-1 expressed very low levels of AR, as measured by qRT-PCR and western blotting (>1000 fold less than the prostate cancer cell line, LNCaP). In contrast, PTC/anaplastic 8505C cells expressed higher levels of AR protein (approximately one third the level expressed in LNCaP cells). Upon addition of androgen, AR in 8505C translocated into the nucleus (as determined by immunocytochemistry) and upregulated transcription of both AR (∼1.7 fold) and FKBP5 (∼1.8 fold). To more fully understand the function of androgen/AR in thyroid cells, the AR cDNA from pSG5-AR was subcloned into the pcDNA3.1+ expression vector and stably transfected into thyroid cell lines. Primers for qRT-PCR of the endogenous or the transfected gene were designed. The 84E7 clone of transfected 8505C cells expressed 68 fold higher levels of AR mRNA than 8505C and 16 fold higher AR protein expression (∼5 fold higher AR protein expression than LNCaP). Upon addition of DHT to clone 84E7, AR translocated into the nucleus, and increased AR and FKBP5 mRNA expression (∼3 fold and ∼13 fold, respectively). The association between androgens/AR and upregulation of FKBP5 in thyroid cancer cells suggests that FKBP5 may play a role in thyroid cancer etiology and the different clinical presentation and outcomes between young women and men/postmenopausal women. Citation Format: Melanie E. MacEwan, Ken Wong, Ismatun Swati, Suqing Xie, Mohammad Rasul, Olena Ardacheva, Joseph Buchsbaum, Edward Shin, Augustine Moscatello, Stimson Schantz, Raj K. Tiwari, Jan Geliebter. FKBP5 is an androgen-responsive gene in thyroid cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3559. doi:10.1158/1538-7445.AM2013-3559