Abstract 3196: The role of Ga12 and Thromboxane receptor beta interaction in bladder cancer progression

Abstract

Abstract In the United States, it is predicted that there will be over 70,000 new cases of bladder cancer this year. Bladder cancer is the fourth most common cancer in men and eighth in women. Our lab has identified that Thromboxane receptor beta (TPβ) plays a role in bladder cancer progression. Our studies have previously shown that TPβ can induce malignant transformation in the immortalized non-transformed bladder cell line, SV-HUC. TPβ is a G-protein coupled receptor that is over-expressed in bladder cancer tumors and high levels of TPβ in bladder cancer patients correlate with decreased survival. G-proteins, such as Gα12, are involved in second messenger cascades that influence a variety of cellular functions, including transcription and motility. Constitutive activation of Gα12 has been shown to induce malignant transformation. Gα12 messenger RNA and protein are expressed in bladder cell lines and paraffin-embedded tissue obtained from bladder cancer patients. This study was designed to elucidate the TPβ and Gα12 dependent pathways that contribute to bladder cancer progression. We found that treatment with TP agonist, U46619, increases cell migration, while treatment with TP antagonist, GR32191, blocks agonist dependent increase in cell migration. We observe that knockdown of Gα12 with shRNA partially reduces U46619-induced cell migration and MAP kinase signaling. Together our results suggest that TPβ mediated malignant phenotypes are in part modulated by Gα12. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3196.