Ression model included age, tumor grade, lymphatic metastasis, clinical stage, and TRPC3 expression levels. In the 90 ovarian cancer tissue samples, using the Cox model, TRPC3 expression levels, lymphatic metastasis, tumor grade and clinical stage were the important parameters for DFS (Table 1A). The hazard ratio (HR) of the high TRPC3 expression group was 2.802 (95 CI: 1.406.586; P=0.003), indicating that recurrence in ovarian cancer patients with high TRPC3 expression was significantly earlier than in patients with low TRPC3 expression (Fig. 8A). The follow-up time and survival status was considered as the overall survival (OS). According to the Cox regression analysis, TRPC3 expression levels, lymphatic metastasis, tumor grade and clinical stage were the most important parameters for the OS; the HR of the high TRPC3 expression group was 2.866 (95 CI: 1.056.777; P=0.039; Table 1B), indicating that high levels of TRPC3 expression were associated with poor overall survival (Fig. 8B). The association of TRPC3 expression levels with poor DFS and OS remained after adjusting for clinical stage (P=0.001 for DFS and P=0.048 for OS; Supplementary Tables 3A and 3B) or for tumor grade (P=0.001 for DFS and P=0.032 for OS; Supplementary Tables 3C and 3D), while the association remained only with poor DFS for lymphatic metastasis (P=0.002; Supplementary Tables 3E). The association was lost with poor OS for lymphatic metastasis (P=0.144; Supplementary Tables 3F), which may be due to an insufficient power for OS analysis; more cases are required for future work. To avoid the influence of pathological type, we performed the same analysis on DFS and OS with tissue samples from 63 serous cancers and found similar patterns (Figs. 8C and 8D).Endocr Relat Cancer. Author manuscript; available in PMC 2014 June 01.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptTao et al.PageThe HR of the high TRPC3 expression group was 4.073 (95 CI: 1.753.462; P=0.001) for DFS and 3.766 (95 CI: 1.0733.226; P=0.039) for OS (Table 1A, 1B). The association of TRPC3 expression levels with poor DFS and OS in serous type also remained after adjusting for clinical stage (P=0.001 for DFS and P=0.041 for OS; Supplementary Tables 4A and 4B) or for tumor grade (P=0.002 for DFS and P=0.045 for OS; Supplementary Tables 4C and 4D). However, the association remained only with poor DFS for lymphatic metastasis (P=0.Streptavidin 001; Supplementary Tables 4E) but was lost with poor OS for lymphatic metastasis (P=0.SARS-CoV-2 S2 Protein (HEK293, His) 079; Supplementary Tables 4F).PMID:24282960 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptDISCUSSIONFSH stimulates proliferation and inhibits apoptosis of ovarian cancer cells, although the mechanism and regulation of FSH are not yet clear. Our previous studies have shown that FSH stimulates the Akt-HIF-1-survivin-VEGF pathway (Huang et al. 2008; Huang et al. 2011). In the present study, we found that TRPC3 is an important molecule that regulates FSH-induced OEC proliferation. We observed that FSH stimulation led to increased TRPC3 protein and mRNA expression levels, facilitating the TRPC3-dependent, agonist-induced Ca2+ influx. Knockdown of TRPC3 inhibited the ability of FSH to stimulate proliferation and block apoptosis of ovarian cancer cells; it also abrogated FSH-induced Akt/PKB phosphorylation, leading to decreased expression of downstream effectors including survivin, HIF1 and VEGF. We observed that this abrogation is partial, suggesting TRPC3 m.
