Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells Journal Article
| Authors: | Maloof, P.; Wang, Q.; Wang, H.; Stein, D.; Denny, T. N.; Yahalom, J.; Fenig, E.; Wieder, R. |
| Article Title: | Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells |
| Abstract: | 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 how 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. |
| Keywords: | controlled study; human cell; proto-oncogene proteins; fluorouracil; flow cytometry; protein localization; cell survival; protein bcl 2; apoptosis; breast cancer; antimetabolites, antineoplastic; nuclear protein; etoposide; antineoplastic agents, phytogenic; down-regulation; tumor cells, cultured; chemosensitivity; breast neoplasms; genetic transduction; fibroblast growth factor 2; messenger rna; immunoprecipitation; immunoblotting; breast epithelium; epithelial cells; immunofluorescence test; cell strain mcf 7; proto-oncogene proteins c-bcl-2; mcf-7 cells; bax; bcl-2; protein bax; bcl-2-associated x protein; basic fibroblast growth factor; cytoplasm protein; tumor stem cells; humans; human; priority journal; article; basic fgf |
| Journal Title: | Breast Cancer Research and Treatment |
| Volume: | 56 |
| Issue: | 2 |
| ISSN: | 0167-6806 |
| Publisher: | Springer |
| Date Published: | 1999-07-01 |
| Start Page: | 153 |
| End Page: | 167 |
| Language: | English |
| PUBMED: | 10573108 |
| PROVIDER: | scopus |
| DOI: | 10.1023/A:1006258510381 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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