Progesterone inhibits human breast cancer cell growth through transcriptional upregulation of the cyclin-dependent kinase inhibitor p27Kip1 gene.
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.
Gizard
Florence
F
UR545 INSERM, Institut Pasteur de Lille and Faculté de Pharmacie, Université de Lille II, France.
Robillard
Romain
R
Gervois
Philippe
P
Faucompré
Anne
A
Révillion
Françoise
F
Peyrat
Jean-Philippe
JP
Hum
W Dean
WD
Staels
Bart
B
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D011374:Progesterone / Q000494:pharmacology / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D011980:Receptors, Progesterone / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation
C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011980:Receptors, Progesterone; D016329:Sp1 Transcription Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011374:Progesterone