PLCε knockdown inhibits prostate cancer cell proliferation via suppression of Notch signalling and nuclear translocation of the androgen receptor

Yin Wang; Xiaohou Wu; Liping Ou; Xue Yang; Xiaorong Wang; Min Tang; E Chen; Chunli Luo

doi:10.1016/j.canlet.2015.03.018

PLCε knockdown inhibits prostate cancer cell proliferation via suppression of Notch signalling and nuclear translocation of the androgen receptor

Cancer Lett. 2015 Jun 28;362(1):61-9. doi: 10.1016/j.canlet.2015.03.018. Epub 2015 Mar 18.

Authors

Yin Wang¹, Xiaohou Wu², Liping Ou¹, Xue Yang¹, Xiaorong Wang¹, Min Tang¹, E Chen¹, Chunli Luo³

Affiliations

¹ Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.
² Department of Urology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
³ Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, China. Electronic address: luochunli79@126.com.

PMID: 25796442
DOI: 10.1016/j.canlet.2015.03.018

Abstract

Phospholipase Cε (PLCε), a key regulator of diverse cellular functions, has been implicated in various malignancies. Indeed, PLCε functions include cell proliferation, apoptosis and malignant transformation. Here, we show that PLCε expression is elevated in prostate cancer (PCa) tissues compared to benign prostate tissues. Furthermore, PLCε depletion using an adenovirally delivered shRNA significantly decreased cell growth and colony formation, arresting the PC3 and LNCaP cell lines in the S phase of the cell cycle. We also observed that PLCε was significantly correlated with Notch1 and androgen receptor (AR). Additionally, we demonstrate that the activation of 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.

Keywords: Androgen receptor; Cell proliferation; Notch1; PLCε; Prostate cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus
Basic Helix-Loop-Helix Transcription Factors / metabolism
Cell Cycle Checkpoints / physiology
Cell Growth Processes / physiology
Cell Line, Tumor
Cell Nucleus / metabolism
Gene Knockdown Techniques
Homeodomain Proteins / metabolism
Humans
Male
Middle Aged
Phosphoinositide Phospholipase C / biosynthesis
Phosphoinositide Phospholipase C / deficiency*
Phosphoinositide Phospholipase C / genetics
Phosphoinositide Phospholipase C / metabolism
Prostatic Neoplasms / enzymology
Prostatic Neoplasms / genetics
Prostatic Neoplasms / metabolism*
Prostatic Neoplasms / pathology*
Prostatic Neoplasms, Castration-Resistant / enzymology
Prostatic Neoplasms, Castration-Resistant / metabolism
Prostatic Neoplasms, Castration-Resistant / pathology
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Receptor, Notch1 / antagonists & inhibitors
Receptor, Notch1 / biosynthesis
Receptor, Notch1 / metabolism*
Receptors, Androgen / biosynthesis
Receptors, Androgen / metabolism*
S Phase / physiology
Signal Transduction
Transcription Factor HES-1

Substances

AR protein, human
Basic Helix-Loop-Helix Transcription Factors
Homeodomain Proteins
NOTCH1 protein, human
RNA, Messenger
Receptor, Notch1
Receptors, Androgen
Transcription Factor HES-1
HES1 protein, human
Phosphoinositide Phospholipase C
phospholipase C epsilon