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

Publication ,  Journal Article
Wang, Q; Maloof, P; Wang, H; Fenig, E; Stein, D; Nichols, G; Denny, TN; Yahalom, J; Wieder, R
Published in: Exp Cell Res
January 10, 1998

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.

Duke Scholars

Published In

Exp Cell Res

DOI

ISSN

0014-4827

Publication Date

January 10, 1998

Volume

238

Issue

1

Start / End Page

177 / 187

Location

United States

Related Subject Headings

  • Tumor Stem Cell Assay
  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins c-bcl-2
  • Mice
  • Kinetics
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Fluorouracil
  • Fibroblast Growth Factor 2
  • Female
 

Citation

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Wang, Q., Maloof, P., Wang, H., Fenig, E., Stein, D., Nichols, G., … Wieder, R. (1998). Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Exp Cell Res, 238(1), 177–187. https://doi.org/10.1006/excr.1997.3820
Wang, Q., P. Maloof, H. Wang, E. Fenig, D. Stein, G. Nichols, T. N. Denny, J. Yahalom, and R. Wieder. “Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.Exp Cell Res 238, no. 1 (January 10, 1998): 177–87. https://doi.org/10.1006/excr.1997.3820.
Wang Q, Maloof P, Wang H, Fenig E, Stein D, Nichols G, et al. Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Exp Cell Res. 1998 Jan 10;238(1):177–87.
Wang, Q., et al. “Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.Exp Cell Res, vol. 238, no. 1, Jan. 1998, pp. 177–87. Pubmed, doi:10.1006/excr.1997.3820.
Wang Q, Maloof P, Wang H, Fenig E, Stein D, Nichols G, Denny TN, Yahalom J, Wieder R. Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Exp Cell Res. 1998 Jan 10;238(1):177–187.
Journal cover image

Published In

Exp Cell Res

DOI

ISSN

0014-4827

Publication Date

January 10, 1998

Volume

238

Issue

1

Start / End Page

177 / 187

Location

United States

Related Subject Headings

  • Tumor Stem Cell Assay
  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins c-bcl-2
  • Mice
  • Kinetics
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Fluorouracil
  • Fibroblast Growth Factor 2
  • Female