Estrogens stimulate the proliferation of human cholangiocarcinoma by inducing the expression and secretion of vascular endothelial growth factor.
Dig Liver Dis
; 41(2): 156-63, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-18395502
ABSTRACT
BACKGROUND:
Estrogens may induce the proliferation of neoplastic cells by activating neo-angiogenesis.AIM:
To evaluate the effect of estrogens on the expression of vascular endothelial growth factor (VEGF) and related receptors (VEGF-R) in human cholangiocarcinoma and the role played by VEGF in mediating the proliferative effects of estrogens.METHODS:
Seven biopsies of intra-hepatic cholangiocarcinoma and the HuH-28 cell lines were investigated. Cell proliferation was measured by both PCNA Western blot and MTS proliferation assay.RESULTS:
By immunohistochemistry, biopsies of human cholangiocarcinoma stained positively for VEGF-A and VEGF-C and related receptors. HuH-28 cells expressed VEGF-A, -C, and VEGFR-1, -2, -3 and, their protein level was enhanced by 17beta-estradiol in association with the stimulation of cell proliferation. 17beta-Estradiol-stimulated proliferation of HuH-28 cells was blocked by 70% by VEGF-TRAP, a receptor-based VEGF inhibitor. 17beta-Estradiol induced the secretion of VEGF in the supernatant of HuH-28 cells. The stimulatory effect of 17beta-estradiol on the protein expression of VEGF-A, VEGF-C and VEGFR-1, -2, -3 was blocked by antagonists of ER (Ici182,780) or insulin-like growth factor 1-receptor (alphaIR3).CONCLUSIONS:
With the limitations of experiments performed in a cell line, our study indicates that VEGF plays a major role in mediating the proliferative effects of estrogens on human cholangiocarcinoma.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias dos Ductos Biliares
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Ductos Biliares Intra-Hepáticos
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Colangiocarcinoma
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Fator A de Crescimento do Endotélio Vascular
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Estradiol
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Estrogênios
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article