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Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.

Publication ,  Journal Article
Maloof, P; Wang, Q; Wang, H; Stein, D; Denny, TN; Yahalom, J; Fenig, E; Wieder, R
Published in: Breast Cancer Res Treat
July 1999

Basic fibroblast growth factor (bFGF, FGF-2), a classical transforming factor, mitogen, and survival factor in multiple cell types, and has a paradoxic role in mammary epithelial cell transformation and proliferation. We have also demonstrated that recombinant FGF-2 uncharacteristically promotes cell death in MCF-7 human breast cancer cells. In this study, we investigated the effects of FGF-2 overexpression on survival in the same MCF-7 cells. In eight breast cancer cell lines and two nontransformed mammary epithelial cell lines, we demonstrated that high levels of Bcl-2 are only expressed in cells with undetectable levels of FGF-2 on western blot. In retrovirally transduced MCF-7 cells expressing both cytoplasm- and nucleus-localizing FGF-2 species and ones expressing only cytoplasm-localizing FGF-2 species, Bcl-2 levels were strongly decreased at both the mRNA and protein levels. Immunoprecipitation of Bax demonstrated a decreased association of Bax with Bcl-2 in these cells. Levels of Bax did not correlate with expression of FGF-2 in the 10 cell lines or in MCF-7 cells. The clonogenic potential of MCF-7 cells in tissue culture was decreased by the expression of FGF-2 and was additively suppressed by the chemotherapeutic agents etoposide and 5-fluorouracil in a dose and time dependent manner. MCF-7 cells overexpressing FGF-2 had a greater rate of programmed cell death at baseline and in response to etoposide and 5-fluorouracil in a TUNEL assay by immunofluorescent microphotography and by flow cytometric quantitation. The pro-apoptotic effect of FGF-2 overexpression on the chemosensitivity of these cells was confirmed by quantitative morphologic determination. These data demonstrate that the expression of FGF-2 downregulates Bcl-2 and promotes programmed cell death in MCF-7 human breast cancer cells.

Duke Scholars

Published In

Breast Cancer Res Treat

DOI

ISSN

0167-6806

Publication Date

July 1999

Volume

56

Issue

2

Start / End Page

153 / 167

Location

Netherlands

Related Subject Headings

  • bcl-2-Associated X Protein
  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Humans
  • Fluorouracil
  • Fibroblast Growth Factor 2
  • Etoposide
 

Citation

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MLA
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Maloof, P., Wang, Q., Wang, H., Stein, D., Denny, T. N., Yahalom, J., … Wieder, R. (1999). Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Breast Cancer Res Treat, 56(2), 153–167. https://doi.org/10.1023/a:1006258510381
Maloof, P., Q. Wang, H. Wang, D. Stein, T. N. Denny, J. Yahalom, E. Fenig, and R. Wieder. “Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.Breast Cancer Res Treat 56, no. 2 (July 1999): 153–67. https://doi.org/10.1023/a:1006258510381.
Maloof P, Wang Q, Wang H, Stein D, Denny TN, Yahalom J, et al. Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Breast Cancer Res Treat. 1999 Jul;56(2):153–67.
Maloof, P., et al. “Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.Breast Cancer Res Treat, vol. 56, no. 2, July 1999, pp. 153–67. Pubmed, doi:10.1023/a:1006258510381.
Maloof P, Wang Q, Wang H, Stein D, Denny TN, Yahalom J, Fenig E, Wieder R. Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Breast Cancer Res Treat. 1999 Jul;56(2):153–167.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

ISSN

0167-6806

Publication Date

July 1999

Volume

56

Issue

2

Start / End Page

153 / 167

Location

Netherlands

Related Subject Headings

  • bcl-2-Associated X Protein
  • Tumor Cells, Cultured
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Humans
  • Fluorouracil
  • Fibroblast Growth Factor 2
  • Etoposide