Fertility and sterility · 2011
All-trans-retinoic acid mediates changes in PI3K and retinoic acid signaling proteins of leiomyomas.
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Ben-Sasson Hadas, Ben-Meir Assaf, Shushan Asher, Karra Laila, Rojansky Nathan, Klein Benjamin Y, Levitzki Rubina, Ben-Bassat Hannah
Аннотация
OBJECTIVE: To detect changes induced by all-trans-retinoic acid (ATRA) on the expression and activation of target proteins of the retinoic acid (RA) and PI3K/Akt pathways involved in leiomyoma growth.
DESIGN: A study on human tissue cultures.
SETTING: Hadassah University Hospital.
PATIENT(S): Premenopausal women with uterine leiomyomas.
INTERVENTION(S): Paired cultures of normal myometrium and leiomyomas, from women undergoing hysterectomy, were obtained.
MAIN OUTCOME MEASURE(S): The effect of ATRA was examined on the expression and phosphorylation of relevant RA, PI3K/Akt, and Bcl2 proteins (immunochemical analysis), cell proliferation, cell cycle distribution, and apoptosis.
RESULT(S): Applying our cell culture model, we demonstrated that ATRA induced changes in the expression and activation of the RA and PI3K/Akt pathway proteins in leiomyoma cells, with significant increases of alcohol dehydrogenase 1 and cyclin D2 protein levels. In part of the leiomyoma cells, ATRA induced a relative increase of Bax (proapoptotic) as well as a relative decrease of phosphorylated glycogen synthase kinase 3β (proapoptotic).
CONCLUSION(S): Our results highlight the involvement of ATRA in the RA and PI3K/Akt pathways, whose specific signaling products may influence the outcome of leiomyoma growth by regulating cell proliferation, apoptosis, and survival. These results might be useful for the on-going research into alternative methods for treating and preventing this disorder.
DESIGN: A study on human tissue cultures.
SETTING: Hadassah University Hospital.
PATIENT(S): Premenopausal women with uterine leiomyomas.
INTERVENTION(S): Paired cultures of normal myometrium and leiomyomas, from women undergoing hysterectomy, were obtained.
MAIN OUTCOME MEASURE(S): The effect of ATRA was examined on the expression and phosphorylation of relevant RA, PI3K/Akt, and Bcl2 proteins (immunochemical analysis), cell proliferation, cell cycle distribution, and apoptosis.
RESULT(S): Applying our cell culture model, we demonstrated that ATRA induced changes in the expression and activation of the RA and PI3K/Akt pathway proteins in leiomyoma cells, with significant increases of alcohol dehydrogenase 1 and cyclin D2 protein levels. In part of the leiomyoma cells, ATRA induced a relative increase of Bax (proapoptotic) as well as a relative decrease of phosphorylated glycogen synthase kinase 3β (proapoptotic).
CONCLUSION(S): Our results highlight the involvement of ATRA in the RA and PI3K/Akt pathways, whose specific signaling products may influence the outcome of leiomyoma growth by regulating cell proliferation, apoptosis, and survival. These results might be useful for the on-going research into alternative methods for treating and preventing this disorder.