Down-regulation of telomerase activity after progesterone treatment of human breast cancer cells: essential role of the cell cycle status.
Steroid hormones have been implicated in the regulation of cellular proliferation and of telomerase activity. Because progestin modulates cell cycle progression in vitro, we investigated if the regulation of telomerase activity by progesterone could be cell cycle-dependent. We found that progesterone treatment of the T47D breast cancer cell line induced both the down-regulation of hTERT (human telomerase reverse transcriptase) mRNA expression and telomerase activity together with a cell cycle blockage characterized by a accumulation of cells in G0/G1-phase. For the first time, after the analysis of cells sorted by flow cytometry, we showed that telomerase activity is lower in the G0/G1-phase than in the S- or G2/M-phase, with or without hormone treatment. These results indicated that the hTERT gene is not a direct target of progesterone; after treatment the down-regulation of telomerase activity is mainly related to the accumulation of cells in the G0/G1-phase of the cell cycle.
Lebeau
Jerome
J
Département de Radiobiologie et Radiopathologie, Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France.
Fouchet
Pierre
P
Ory
Katherine
K
Chevillard
Sylvie
S
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D011374:Progesterone; D019098:Telomerase