Fibroblast growth factor 2 promotes tumor progression in an autochthonous mouse model of prostate cancer

Nathaniel Polnaszek, Bernard Kwabi-Addo, Leif E. Peterson, Mustafa Ozen, Norman M. Greenberg, Sagrario Ortega, Claudio Basilico, Michael Ittmann

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Fibroblast growth factor (FGF) 2 (or basic FGF) is expressed at increased levels in human prostate cancer. FGF2 can promote cell motility and proliferation, increase tumor angiogenesis, and inhibit apoptosis, all of which play an important role in tumor progression. To determine whether FGF2 plays a critical role in prostate cancer progression, we have used the transgenic adenocarcinoma of the mouse prostate (TRAMP) model system. A high percentage of TRAMP mice develop metastatic prostate cancer, and thus the TRAMP model is useful for evaluating cancer progression. TRAMP mice were crossed with FGF2 knockout (FGF2-/-) mice, and tumor progression in TRAMP mice that were either hemi- or homozygous for inactivation of the FGF2 allele was compared with progression in wild-type TRAMP mice. Inactivation of even one FGF2 allele resulted in increased survival, a decrease in metastasis, and inhibition of progression to the poorly differentiated phenotype in primary prostatic tumors. When compared with wild-type mice, poorly differentiated tumors arising in FGF+/- and FGF-/- mice expressed higher levels of vascular endothelial growth factor and, in some cases, increased levels of acidic FGF intracellular binding protein, a nuclear FGF1-binding protein. These findings suggest that both FGF2-mediated angiogenesis and intranuclear FGF2 activities may promote tumor progression and support the hypothesis that FGF2 plays a significant role in prostate cancer progression in vivo.

Original languageEnglish (US)
Pages (from-to)5754-5760
Number of pages7
JournalCancer research
Volume63
Issue number18
StatePublished - Sep 15 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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