当前位置： SCI文献检索 > BRITISH JOURNAL OF CANCER期刊下所有文献 > Expression of two WFDC1/ps20 isoforms in prostate stromal cells induces paracrine apoptosis through regulation of PTGS2/COX-2.

Expression of two WFDC1/ps20 isoforms in prostate stromal cells induces paracrine apoptosis through regulation of PTGS2/COX-2.

Abstract：

BACKGROUND:WFDC1/Prostate stromal 20 (ps20) is a small secreted protein highly expressed within the prostate stroma. WFDC1/ps20 expression is frequently downregulated or lost in prostate cancer (PCa) and ps20 has demonstrated growth-suppressive functions in numerous tumour model systems, although the mechanisms of this phenomenon are not understood. METHODS:Ps20 was cloned and overexpressed in DU145, PC3, LNCaP and WPMY-1 cells. Cellular growth, cell cycle and apoptosis were characterised. WPMY-1 stromal cells expressing ps20 were characterised by transcriptome microarray and the function of WPMY-1 conditioned media on growth of PCa cell lines was assessed. RESULTS:Prostrate stromal 20 expression enhanced the proliferation of LNCaP cells, whereas stromal WPMY-1 cells were inhibited and underwent increased apoptosis. Prostrate stromal 20-expressing WPMY-1 cells secrete a potently proapoptotic conditioned media. Prostrate stromal 20 overexpression upregulates expression of cyclooxygenase-2 (COX-2) in LNCaP and WPMY-1 cells, and induces expression of a growth-suppressive phenotype, which inhibits proliferation of PCa cells by ps20-expressing WPMY-1 conditioned media. This growth suppression was subsequently shown to be dependent on COX-2 function. CONCLUSIONS:This work posits that expression of ps20 in the prostate stroma can regulate growth of epithelial and other tissues through the prostaglandin synthase pathway, and thereby restricts development and progression of neoplasms. This provides a rational for selective pressure against ps20 expression in tumour- associated stroma.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Hickman OJ,Smith RA,Dasgupta P,Rao SN,Nayak S,Sreenivasan S,Vyakarnam A,Galustian C

doi

10.1038/bjc.2016.91

subject

Has Abstract

pub_date

2016-05-24 00:00:00

pages

1235-42

issue

11

eissn

0007-0920

issn

1532-1827

pii

bjc201691

journal_volume

114

pub_type

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