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Effect of keratinocyte growth factor on cell viability in primary cultured human prostate cancer stromal cells. J Steroid Biochem Mol Biol 2006 Jul;100(1-3):24-33

Date

07/21/2006

Pubmed ID

16854582

DOI

10.1016/j.jsbmb.2006.03.005

Scopus ID

2-s2.0-33745980188   16 Citations

Abstract

In normal prostate, keratinocyte growth factor (KGF), also known as fibroblast growth factor-7 (FGF-7) serves as a paracrine growth factor synthesized in stromal cells that acts on epithelial cells through its receptor, KGFR. KGF and KGFR were found in human cancer epithelial cells as well as stromal cells. Since KGF expressed in epithelial cells of benign prostatic hyperplasia (BPH) and in prostate cancer, it has been suggested that KGF might act as an autocrine factor in BPH and prostate cancer. To investigate the roles of KGF in cancerous stroma, primary cultured human prostate cancer stromal cells (PCSCs) were isolated and evaluated. These PCSCs possessed estrogen receptors and KGFR, but not androgen receptor as determined by RT-PCR and Western blot, respectively. KGF exhibited mitogenic and anti-apoptotic effects that correlated with induction of cyclin-D1, Bcl-2, Bcl-xL and phospho-Akt expression in PCSCs, where treatment with KGF antiserum abolished cell proliferation and anti-apoptotic protein expression. PCSCs exposed to KGF for various time periods resulted in phosphorylation of Akt and subsequent up-regulation of Bcl-2. KGF modulated dynamic protein expression indicated that KGF triggered cell cycle machinery and then activated anti-apoptotic actions in PCSCs. Cell proliferation analysis indicated that tamoxifen or ICI 182,780 reduced cell viability in a dose-dependent manner; however, KGF prevented this inhibition, which further demonstrated KGF triggered anti-apoptotic machinery through activating Bcl-2 and phospho-Akt expression. In summary, KGF has an autocrine effect and serves as a survival factor in primary cultured human prostate cancer stromal cells.

Author List

Huang YW, Wang LS, Chang HL, Ye W, Shu S, Sugimoto Y, Lin YC

Authors

Yi-Wen Huang PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Li-Shu Wang PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Survival
Cells, Cultured
Dose-Response Relationship, Drug
Fibroblast Growth Factor 7
Humans
Immunohistochemistry
Male
Prostatic Neoplasms
Receptors, Estrogen
Receptors, Fibroblast Growth Factor
Stromal Cells
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1