QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online March 22, 2006
doi: 10.1242/10.1242/jcs.02802

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heer, R. Articles by Leung, H. Y. Search for Related Content PubMed PubMed Citation Articles by Heer, R. Articles by Leung, H. Y. Social Bookmarking                         What's this?

KGF suppresses ₂ß₁ integrin function and promotes differentiation of the transient amplifying population in human prostatic epithelium

¹ Urology Research Group, Northern Institute for Cancer Research, University of Newcastle, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
² YCR Cancer Research Unit (Area Department of Biology, University of York, PO Box 373, York, YO10 5DD, UK
³ FACS laboratory, Surgical and Reproductive Sciences, University of Newcastle, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK

^* Author for correspondence (e-mail: rakesh.heer{at}ncl.ac.uk)

Accepted 22 November 2005

Prostate epithelial stem cells are self-renewing cells capable of differentiation into prostate epithelium, and are thought to contribute towards both benign and malignant conditions in the human prostate. We have previously demonstrated that prostate epithelial basal cells express high levels of integrin ₂ß₁ and this population can be subdivided into stem (₂ß₁^hi CD133⁺) and transient-amplifying population (TAP) cells (₂ß₁^hi CD133^-). However, the molecular mechanism(s) controlling the commitment and regulation of these cells towards differentiated epithelium remains unclear. Here, we demonstrate that ß₁ integrin function is required for the maintenance of basal prostatic epithelial cells and suppression of its function by either methylcellulose or, more specifically, ß₁-blocking antibody (80 µg/ml) induces differentiation, with associated expression of the differentiation-specific markers prostate acid phosphatase (PAP) and cytokeratin 18 (CK18). Keratinocyte growth factor (KGF), a stromal-derived growth factor, has previously been implicated in prostate organogenesis using in vitro tissue recombination experiments. We show that treatment with KGF (10 ng/ml) potently induces epithelial differentiation with concomitant suppression of ₂ß₁ integrin expression as well as the induction of androgen receptor expression. Specifically, p38-MAPK appears to be involved and the presence of SB202190, a p38 inhibitor, significantly blocks KGF-induced differentiation. Furthermore, the expression of the high-affinity receptor tyrosine kinase to KGF (FGFR2) is predominantly detectable in ₂ß₁^hi CD133^- TAP cells when compared with stem cells (₂ß₁^hi CD133⁺), which would therefore be relatively unresponsive to the differentiating effect of KGF. Taken together, using a human primary culture model, we have demonstrated key roles for interactions between KGF and integrin-mediated function in the regulation of prostate epithelial differentiation.

Key words: Stem cells, Transient amplifying cells, Prostate, Epithelia, ß₁ integrin, p38, KGF

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Mimeault, P. P. Mehta, R. Hauke, and S. K. Batra Functions of Normal and Malignant Prostatic Stem/Progenitor Cells in Tissue Regeneration and Cancer Progression and Novel Targeting Therapies Endocr. Rev., April 1, 2008; 29(2): 234 - 252. [Abstract] [Full Text] [PDF]

				P. Koria and S. T. Andreadis KGF promotes integrin {alpha}5 expression through CCAAT/enhancer-binding protein-beta Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1020 - C1031. [Abstract] [Full Text] [PDF]

				B. N. Gomperts, J. A. Belperio, M. C. Fishbein, M. P. Keane, M. D. Burdick, and R. M. Strieter Keratinocyte Growth Factor Improves Repair in the Injured Tracheal Epithelium Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 48 - 56. [Abstract] [Full Text] [PDF]

				Y. Lin, G. Liu, Y. Zhang, Y.-P. Hu, K. Yu, C. Lin, K. McKeehan, J. W. Xuan, D. M. Ornitz, M. M. Shen, et al. Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis Development, February 15, 2007; 134(4): 723 - 734. [Abstract] [Full Text] [PDF]