Prostate cancer (PC) is the second leading cause of cancer-related death among men. The standard of care for locally advanced PC is androgen deprivation (AD) therapy, which eventually fails, leading to incurable and terminal castration resistant PC (CRPC). CRPC has few therapeutic options, due to the limited molecular understanding of its origins. Through transcriptomics of a novel early CRPC line developed in the Rai lab, it was discovered that the vasodilatory nitric oxide receptor complex, soluble guanylyl cyclase (sGC), is downregulated in CRPC. We hypothesize that elevating sGC signaling through FDA-approved agonists will limit CRPC growth. sGC is a heterodimeric protein that consists of two subunits: GC1α (GUCY1A1) and GC1ꞵ (GUCY1B1). In order to respond to sGC agonists, the complex must be intact, requiring both subunits to be expressed at some relatively equivalent threshold level. Therefore, we analyzed sGC subunit expression levels in cancer cell lines at different stages of CRPC progression, using quantitative PCR (qPCR) to measure mRNA and immunoblotting to measure protein expression. We find that progression to CRPC is associated with striking dysregulation of the subunits with GC1ꞵ either significantly higher or lower than GC1α. This data will be used to determine the extent to which agonists stimulate sGC activity, to identify threshold levels of subunits that will enable robust response in CRPC patients.
