Basic fibroblast growth factor confers a less malignant phenotype in MDA-MB-231 human breast cancer cells

Reju M. Korah, Vilayvanh Sysounthone, Yosef Golowa, Robert Wieder

Research output: Contribution to journalArticle

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Abstract

Basic fibroblast growth factor (FGF-2) expression is associated with a more differentiated phenotype, earlier stage of disease, and a better prognosis in breast cancer patients. To determine whether expression of FGF-2 can cause a less malignant phenotype, we engineered MDA-MB-231 cells, a highly dedifferentiated, invasive breast cancer cell line, to express different isoforms of FGF-2. Cells expressed either cytoplasmic, nuclear, or a combination of both FGF-2 isoforms. Western blots of 2 M NaCl washes and of conditioned medium demonstrated that these cells did not export FGF-2. Cells expressing FGF-2 had levels of fibroblast growth factor receptors equivalent with those of control cells. Transformation was assayed by anchorage- independent colony formation and tumor formation in athymic mice. All of the constructs expressing various FGF-2 isoforms had a 60-70% reduction in colony formation in soft agar, but only cells expressing the M(r) 18,000 FGF-2 isoform formed fewer and smaller tumors in mice. To determine potential mechanisms responsible for a less malignant phenotype, experiments measuring invasion in Matrigel, the secretion of matrix metalloprotease activity and migration in a modified Boyden chamber and in a patch wound motility assay were carried out. Cells expressing the M(r) 18,000 cytoplasmic FGF-2 moiety had a 45% decrease in invasion in Matrigel compared to vector-transfected controls. Cells expressing M(r) 18,000 FGF-2 had an increase in M(r) 97,000 and M(r) 48,000 collagenase, demonstrating that the decreased invasive potential was not due to a down-regulation of gelatinolytic or caseinolytic matrix metalloproteinases. However, motility was decreased in both assays, primarily in cells expressing M(r) 18,000 FGF-2, whereas exogenous recombinant human FGF-2 had no effect. These studies demonstrate for the first time that FGF-2 expression can cause a less malignant phenotype in breast cancer cells, possibly as a result of decreased motility and invasion.

Original languageEnglish (US)
Pages (from-to)733-740
Number of pages8
JournalCancer Research
Volume60
Issue number3
StatePublished - Feb 1 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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