Fibroblast growth factor 2 promotes tumor progression in an autochthonous mouse model of prostate cancer.
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.
Polnaszek
Nathaniel
N
Department of Pathology, Baylor College of Medicine and Houston Department of Veterans Affairs Medical Center, Houston, Texas 77030, USA.
Kwabi-Addo
Bernard
B
Peterson
Leif E
LE
Ozen
Mustafa
M
Greenberg
Norman M
NM
Ortega
Sagrario
S
Basilico
Claudio
C
Ittmann
Michael
M
D000483:Alleles; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1