Related Experiment Video
Updated: Aug 14, 2026
Spheroid Assay to Measure TGF-β-induced Invasion
Published on: November 16, 2011
Progression in MCF-7 breast cancer cell tumorigenicity: compared effect of FGF-3 and FGF-4
A Hajitou1, C Deroanne, A Noël
1Laboratories of Fundamental Virology, University of Liege, Belgium.
Abstract:
The transforming properties of fibroblast growth factor 3 (FGF-3) were investigated in MCF7 breast cancer cells and compared to those of FGF-4, a known oncogenic product. The short form of fgf-3 and the fgf-4 sequences were each introduced with retroviral vectors and the proteins were only detected in the cytoplasm of the infected cells, as expected. In vitro, cells producing FGF-3 (MCF7.fgf-3) and FGF-4 (MCF7.fgf-4) displayed an amount of estrogen receptors decreased to around 45% of the control value. However, MCF7.fgf-3 cell proliferation remained responsive to estradiol supply. The sensitivity of the MCF7.fgf-4 cells, if existant, was masked by the important mitogenic action exerted by FGF-4. In vivo, the MCF7.fgf-3 and MCF7.fgf-4 cells gave rise to tumors under conditions in which the control cells were not tumorigenic. Supplementing the mice with estrogen had the paradoxical effect of totally suppressing the start of the FGF-3 as well as the FGF-4 tumors. Tumorigenicity in the presence of matrigel was similar for MCF7.fgf-3 and control cells and was increased by estrogen supplementation. Once started, the MCF7.fgf-4 tumors grew with a characteristic high rate. Remarkably, FGF-4 but not FGF-3, stimulated the secretion of vascular endothelial growth factor (VEGF165) without altering the steady-state level of its mRNA, suggesting a possible regulation of VEGF synthesis at the translational level in MCF7 cells. The increased VEGF secretion is probably involved in the more aggressive phenotype of the MCF7.fgf-4 cells while a decreased dependence upon micro-environmental factors might be part of the increased tumorigenic potential of the MCF7.fgf-3 cells.
Insights
Fibroblast growth factor 3 (FGF-3) and FGF-4 promote tumor formation in breast cancer cells. FGF-4 enhances tumor aggressiveness by increasing vascular endothelial growth factor (VEGF) secretion.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Fibroblast growth factors (FGFs) play roles in cell growth and differentiation.
- FGF-3 and FGF-4 are implicated in cancer, but their specific transforming properties in breast cancer require detailed investigation.
Purpose of the Study:
- To compare the transforming properties of fibroblast growth factor 3 (FGF-3) and fibroblast growth factor 4 (FGF-4) in MCF7 breast cancer cells.
- To elucidate the in vitro and in vivo effects of FGF-3 and FGF-4 on cell proliferation, estrogen receptor levels, and tumorigenicity.
Main Methods:
- Retroviral vectors were used to introduce FGF-3 and FGF-4 sequences into MCF7 cells.
- In vitro proliferation assays and in vivo tumor formation studies were conducted.
- Estrogen receptor levels and vascular endothelial growth factor (VEGF) secretion were analyzed.
Main Results:
- Both FGF-3 and FGF-4 reduced estrogen receptor levels in MCF7 cells.
- MCF7 cells expressing FGF-3 and FGF-4 exhibited increased tumorigenicity in vivo.
- FGF-4, but not FGF-3, significantly stimulated VEGF165 secretion, suggesting translational regulation.
- Estrogen supplementation paradoxically suppressed tumor initiation for both FGF-3 and FGF-4 expressing cells.
Conclusions:
- FGF-3 and FGF-4 possess transforming properties, contributing to the tumorigenicity of MCF7 breast cancer cells.
- FGF-4's aggressive phenotype may be mediated by increased VEGF secretion, while FGF-3's tumorigenicity might stem from reduced dependence on micro-environmental factors.
- The paradoxical effect of estrogen on tumor initiation warrants further investigation.
