Plce Knockdown Inhibits Prostate Cancer Cell Proliferation Via Suppression Of Notch Signalling And Nuclear Translocation Of The Androgen Receptor

Objective:To investigate PLCε expression in prostate tissue and its clinical significance. To explore the function of PLCs in prostate cancer cell proliferation and its molecular mechanism.Methods:PLCε, Notchl and AR expressions have been detected by immunohistochemistry staining in 57 human prostate tissue specimens (10 normal prostate tissues,10 BPH tissues and 37 prostate cancer tissues) and the correlation of PLCε expression and clinical pathological parameters has been analysed statistically. After infecting prostate cancer cell lines (PC-3 and LNCaP) with Ad-shPLCε, MTT assay and colony formation test were used to evaluate the cell proliferation; real-time quantitative PCR and western blotting were used to detect mRNA and protein expressions of PLCε, cyclinD1, PCNA and c-fos; flow cytometry was used to detect cell cycles; immunocytochemistry method was used to evaluate AR expression in prostate cancer cells; after activating or inactivating Notch and AR signalling with adenovirus or medicine respectively, western blotting were used to detect protein expressions of Notch 1, Hesl, AR and PSA.Results:PLCε, Notchl and AR expressions are elevated in prostate cancer (PCa) tissues compared to benign prostate tissues (P＜0.001). Furthermore, PLCε depletion using an adenovirally delivered shRNA significantly decreased cell proliferation (P＜0.05), arresting the PC3 and LNCaP cell lines in the S phase of the cell cycle (P<0.05), suppressing Notch signalling and AR nuclear tranlocation.Conclusion:PLCe was highly expressed in prostate cancer tissues. Both the Notch and AR signalling pathways is involved in PLCε-mediated oncogenic effects in PCa. Our findings suggest that PLCε is a putative oncogene and prognostic marker, potentially representing a novel therapeutic target for PCa.