CXCL13 mediates prostate cancer cell proliferation through JNK signalling and invasion through ERK activation.

Abstract:

OBJECTIVES:  The focus of this study was to determine the dedicator of cytokinesis 2 (DOCK2), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase-1 (JNK) and Akt signals involved in CXCL13-mediated prostate cancer (PCa) cell invasion and proliferation. MATERIALS AND METHODS:  Androgen-sensitive (LNCaP), hormone-refractory (PC3) cells and normal cells (RWPE-1) were used to determine CXCL13-mediated PCa cell invasion and proliferation. Immuno-blotting, fast activated cell-based (FACE) ELISA, caspase activity, cell invasion and proliferation assays were performed to ascertain some of the signalling events involved in PCa cell proliferation and invasion. RESULTS:  Unlike androgen-sensitive LNCaP cells, we report for the first time that the hormone-refractory cell line, PC3, expresses DOCK2. CXCL13-mediated LNCaP and PC3 cell invasion was regulated by Akt and ERK1/2 activation in a DOCK2-independent fashion. CXCL13 also promoted LNCaP cell proliferation in a JNK-dependent fashion even in the absence of DOCK2. In contrast, CXCL13 induced PC3 cell proliferation through JNK activation, which required DOCK2. CONCLUSIONS:  Our results show CXCL13-mediated PCa cell invasion requires Akt and ERK1/2 activation and suggests a new role for DOCK2 in proliferation of hormone-refractory CXCR5-positive PCa cells.

journal_name

Cell Prolif

journal_title

Cell proliferation

authors

El-Haibi CP,Singh R,Sharma PK,Singh S,Lillard JW Jr

doi

10.1111/j.1365-2184.2011.00757.x

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

311-9

issue

4

eissn

0960-7722

issn

1365-2184

journal_volume

44

pub_type

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