Bisphenol A induces human uterine leiomyoma cell proliferation through membrane-associated ERα36 via nongenomic signaling pathways.
Mol Cell Endocrinol
; 484: 59-68, 2019 03 15.
Article
en En
| MEDLINE
| ID: mdl-30615907
ABSTRACT
The role of ERα36 in regulating BPA's effects and its potential as a risk factor for human uterine fibroids were evaluated. BPA at low concentrations (10-6⯵M - 10⯵M) increased proliferation by facilitating progression of hormonally regulated, immortalized human uterine leiomyoma (ht-UtLM; fibroid) cells from G0-G1 into S phase of the cell cycle; whereas, higher concentrations (100⯵M-200⯵M) decreased growth. BPA upregulated ERα36 gene and protein expression, and induced increased SOS1 and Grb2 protein expression, both of which are mediators of the MAPKp44/42/ERK1/2 pathway. EGFR (pEGFR), Ras, and MAPKp44/42 were phosphorylated with concurrent Src activation in ht-UtLM cells within 10â¯min of BPA exposure. BPA enhanced colocalization of phosphorylated Src (pSrc) to ERα36 and coimmunoprecipitation of pSrc with pEGFR. Silencing ERα36 with siERα36 abolished the above effects. BPA induced proliferation in ht-UtLM cells through membrane-associated ERα36 with activation of Src, EGFR, Ras, and MAPK nongenomic signaling pathways.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fenoles
/
Compuestos de Bencidrilo
/
Receptor alfa de Estrógeno
/
Leiomioma
Tipo de estudio:
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article