当前位置： SCI文献检索 > EXPERIMENTAL CELL RESEARCH期刊下所有文献 > Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.

Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.

Abstract：

:Basic fibroblast growth factor (bFGF) is a mitogen and a survival factor in fibroblasts and endothelial cells. It acts as an angiogenesis factor in breast cancer, but paradoxically inhibits proliferation in several breast cancer cell lines. In this study, we investigated the effects of bFGF on the survival of MCF-7 human breast cancer cells in order to determine if these effects were also opposite to those in fibroblasts. Incubation of NIH 3T3 cells with bFGF for 24 h caused an approximately 30% increase in day 12 +/- 2 adherent colonies while causing an approximately 50% decrease in MCF-7 colony formation. Incubation of NIH 3T3 cells with bFGF prior to etoposide or 5-fluorouracil treatment caused a proportionally smaller decrease in colony forming efficiency as a result of drug treatment, while preincubation of MCF-7 cells with bFGF caused a similar but opposite additive increase in drug-induced diminution of colony forming efficiency. These effects on MCF-7 cells were observed at variable times of incubation and doses of etoposide to 1 microM and 5-fluorouracil to 200 microM and at variable times of incubation and concentrations of bFGF to 1 ng/ml. Incubating with bFGF after drug exposure had similar effects on the reduction of cloning efficiency. The effects of bFGF were similar on programmed cell death, as determined by morphologic characteristics of apoptosis on 400 cell counts and FITC-dUTP 3'-OH DNA end labeling. Basic FGF promoted apoptosis and increased the rate of drug-induced cell death with both etoposide and 5-fluorouracil. While recombinant bFGF affected Bcl-2 protein and mRNA levels in NIH 3T3 cells only marginally and variably and had no discernible effects on Bax protein levels, it markedly downregulated Bcl-2 mRNA and protein levels in MCF-7 cells and caused an increase in Bax protein levels. These changes resulted in a decreased association of Bcl-2 with immunoprecipitable Bax and an increased association of Bax with immunoprecipitable Bcl-2 in MCF-7 cells treated with bFGF. These data suggest that bFGF may cause different phenotypic responses in breast cancer cells from those in surrounding cells and offer one possible mechanism through opposite regulation of Bcl-2 and Bax. Inhibition of colony formation by bFGF was observed in several breast cancer cells lines, demonstrating that this effect demonstrated in MCF-7 cells was more universal.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Wang Q,Maloof P,Wang H,Fenig E,Stein D,Nichols G,Denny TN,Yahalom J,Wieder R

doi

10.1006/excr.1997.3820

subject

Has Abstract

pub_date

1998-01-10 00:00:00

pages

177-87

issue

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(97)93820-9

journal_volume

238

pub_type

杂志文章

在线工具

Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.