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Dehydroepiandrosterone inhibits the proliferation of human umbilical vein endothelial cells by enhancing the expression of p53 and p21, restricting the phosphorylation of retinoblastoma protein, and is androgen‐ and estrogen‐receptor independent
Author(s) -
Zapata Estrella,
Ventura José L.,
De la Cruz Karina,
Rodriguez Emma,
Damián Pablo,
Massó Felipe,
Montaño Luis F.,
LópezMarure Rebeca
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04563.x
Subject(s) - dehydroepiandrosterone , umbilical vein , endocrinology , medicine , androgen , androgen receptor , estrogen , retinoblastoma protein , phosphorylation , estrogen receptor , biology , cell growth , chemistry , apoptosis , cell cycle , microbiology and biotechnology , hormone , biochemistry , cancer , prostate cancer , breast cancer , in vitro
Dehydroepiandrosterone (DHEA), a steroid hormone, modified the proliferation of human umbilical vein endothelial cells in a dose‐dependent manner. Its inactive sulfate ester (DHEA‐S) and two of its metabolites – estradiol and testosterone – had no inhibitory effect at physiological concentrations. Antiproliferation was associated with arrest in the G1 phase of the cell cycle, but not with cell death, as evaluated by cleavage of poly(ADP‐ribose) polymerase and exposure of phosphatidylserine. The effect was not blocked by inhibitors of androgen or estrogen receptors. DHEA diminished the levels of phosphorylated retinoblastoma protein and increased the expression of p53 and p21 mRNAs. These results show that DHEA inhibits endothelial cell proliferation by regulating cell cycle relevant proteins through a cytoplasmic steroid hormone‐independent pathway.