Requirements of phosphatidylinositol-3 kinase and mammalian target of rapamycin for estrogen-induced proliferation in uterine leiomyoma- and myometrium-derived cell lines.
OBJECTIVE
This study was undertaken to investigate the effects of 17beta-estradiol (E2) on G1 cell cycle progression and proliferation in uterine fibroid and myometrial cells and the roles of phosphatidylinositol-3 kinase and mammalian target of rapamycin in mediating these estrogen effects.


METHODS
The human uterine smooth muscle-derived cells (UtSM) and uterine leiomyoma-derived cells (UtLM) were treated with varying doses of E2 with or without pretreatment with LY294002, a phosphatidylinositol-3 kinase inhibitor, or rapamycin, a mammalian target of rapamycin inhibitor. The effects of E2 on cell cycle progression and proliferation and the roles of phosphatidylinositol-3 kinase and mammalian target of rapamycin in E2-induced effects were studied.


RESULTS
Compared with controls, E2 significantly induced G1 cell cycle progression and proliferation in uterine smooth muscle-derived cells and uterine leiomyoma-derived cells. These effects, however, were significantly blocked when LY294002 or rapamycin was used.


CONCLUSIONS
E2 significantly induces G1 cell cycle progression and cell proliferation in uterine smooth muscle-derived cells and uterine leiomyoma-derived cells, in which phosphatidylinositol-3 kinase and mammalian target of rapamycin are essentially required.
Yin
Xuejun J
XJ
Department of Pathology, West Virginia University, Morgantown, WV 26506-9203, USA.
Wang
Gangduo
G
Khan-Dawood
Firyal S
FS
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D007889:Leiomyoma / Q000201:enzymology*; D009025:Morpholines / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014594:Uterine Neoplasms / Q000201:enzymology*
D002867:Chromones; D004791:Enzyme Inhibitors; D004958:Estradiol; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human