Abstract 3926: RhoB expression is upregulated by androgen in thyroid cancer cells

Abstract

Abstract The incidence of thyroid cancer has increased three-fold over the last thirty years and the American Cancer Society estimates that there will be 62,980 new cases and 1,890 deaths due to the disease in the United States in 2014. Papillary Thyroid Cancer (PTC) is the most common endocrine malignancy and develops in premenopausal women, at a four-fold higher incidence, than in men. However, PTC exhibits increased aggressiveness with poor prognosis in men diagnosed with the disease. These observations led us to explore the role of androgen and androgen receptor in this disease. Preliminary data from our lab indicates that androgen receptor (AR) acts as a negative regulator of growth as evidenced by a statistically significant decrease in proliferation upon DHT addition to 8505c anaplastic/PTC cells stably transfected with AR. Transcriptional profiling using RNA-Seq and gene ontology analysis, on a 48 hour DHT treated 8505c-AR transfected clone, 84E7, revealed significant changes in the expression of genes associated with proliferation (474 genes, p = 2.4E-24), cell cycle progression (129 genes, p = 6.54E-6) and migration (301 genes, p = 3.77E-30). Amongst the genes which showed the highest significant differential expression was RhoB, a Rho GTPase, with an approximately 50-fold upregulation. Rho proteins are small molecules belonging to the Ras superfamily, known to regulate cell morphology, actin/microtubule cytoskeleton reorganization along with vesicle trafficking. While RhoA and RhoC promote cancer progression and metastasis, the functions of their structural homolog, RhoB, are largely context dependent. Evidence has emerged that RhoB expression may support malignancy in certain cancers, while exhibiting a tumor-suppressor gene function in others. In our system, addition of DHT to 84E7 cells for short time periods of 1, 3 and 6 hours resulted in rapid RhoB mRNA upregulation by 2.5, 8, and 17 fold, respectively, compared to untreated cells. This quick, time-dependent increase in androgen-responsive RhoB may play an integral protective and reparative role which is possibly lost during neoplasticity of thyrocytes. Investigations into various pathways linking RhoB and effector proteins with carcinogenesis would be crucial in assessing the potential of RhoB as a bio-marker for metastatic PTC and thence opening avenues for development of viable therapies for better management of the disease. Citation Format: Anvita Gupta, Melanie Jones, Augustine Moscatello, Edward Shin, Raj K. Tiwari, Jan Geliebter. RhoB expression is upregulated by androgen in thyroid cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3926. doi:10.1158/1538-7445.AM2015-3926