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Progesterone inhibits human breast cancer cell growth through transcriptional upregulation of the cyclin‐dependent kinase inhibitor p27 Kip1 gene
Author(s) -
Gizard Florence,
Robillard Romain,
Gervois Philippe,
Faucompré Anne,
Révillion Françoise,
Peyrat Jean-Philippe,
Hum W. Dean,
Staels Bart
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.08.084
Subject(s) - downregulation and upregulation , kinase , cancer research , cyclin , human breast , cell growth , gene , chemistry , cyclin dependent kinase 4 , breast cancer , cyclin d1 , cyclin dependent kinase 2 , cell cycle , cyclin dependent kinase , cell cycle progression , microbiology and biotechnology , cancer , biology , genetics , biochemistry
The effects of progesterone derivatives on breast cancer development are still controversial, probably accounting for their biphasic, opposed effects on mammary cell‐cycle regulation. Here, we demonstrate in vitro that the growth‐inhibitory effects of progesterone on breast cancer T‐47D cells require the transcriptional upregulation of the cyclin‐dependent kinase inhibitor p27 Kip1 (p27) gene. A statistical analysis of human tumor biopsies further indicates that p27 mRNA levels correlate to progesterone receptor (PR) levels. Moreover, p27 gene expression is inversely associated with tumor aggressiveness, and is a prognostic factor of favorable disease outcome. Thus, progesterone derivatives selectively activating the p27 gene promoter could be promising drugs against breast cancer progression.