All-trans-retinoic acid mediates changes in PI3K and retinoic acid signaling proteins of leiomyomas

Riferimento: 
Fertil Steril. 2011 May;95(6):2080-6.
Autori: 
Ben-Sasson H, Ben-Meir A, Shushan A, Karra L, Rojansky N, Klein BY, Levitzki R, Ben-Bassat H.
Fonte: 
Fertil Steril. 2011 May;95(6):2080-6.
Anno: 
2011
Azione: 
Il coinvolgimento dell'acido all-trans-retinoico (ATRA) sui percorsi di RA e PI3K/Akt, può influenzare la crescita del leiomioma con regolazione della proliferazione cellulare, apoptosi, e sopravvivenza.
Target: 
ATRA – RA – PI3K/Akt/leiomioma.

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.

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