Hepatocyte Growth Factor and Vitamin D Cooperatively Inhibit Androgen-Unresponsive Prostate Cancer Cell Lines1
Expression of MET, the receptor for hepatocyte growth factor (HGF), has been associated with androgen-insensitive prostate cancer. In this study we evaluated MET activation by HGF and HGF action in prostate cancer cell lines. HGF causes phosphorylation (activation) of the MET receptor in three andro...
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Published in | Endocrinology (Philadelphia) Vol. 141; no. 7; pp. 2567 - 2573 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.07.2000
|
Online Access | Get full text |
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Summary: | Expression of MET, the receptor for hepatocyte growth factor (HGF), has
been associated with androgen-insensitive prostate cancer. In this
study we evaluated MET activation by HGF and HGF action in prostate
cancer cell lines. HGF causes phosphorylation (activation) of the MET
receptor in three androgen-unresponsive cell lines (DU 145, PC-3, and
ALVA-31) together with morphological change. Although HGF is known to
stimulate the growth of normal epithelial cells, including those from
prostate, we found that HGF inhibited ALVA-31 and DU 145
(hormone-refractory) cell lines. Moreover, HGF and vitamin D additively
inhibited growth in each androgen-unresponsive cell line, with the
greatest growth inhibition in ALVA-31 cells. Further studies in ALVA-31
cells revealed distinct cooperative actions of HGF and vitamin D. In
contrast to the accumulation of cells in G1 seen during
vitamin D inhibition of androgen-responsive cells (LNCaP), growth
inhibition of the androgen-unresponsive ALVA-31 cell line with the HGF
and vitamin D combination decreased, rather than increased, the
fraction of cells in G1, with a corresponding increase in
the later cell cycle phases. This cell cycle redistribution suggests
that in androgen-unresponsive prostate cancer cells, HGF and vitamin D
act together to slow cell cycle progression via control at sites beyond
the G1/S checkpoint, the major regulatory locus of growth
control in androgen-sensitive prostate cells. |
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ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.141.7.7546 |