Polnaszek Nathaniel, Kwabi-Addo Bernard, Peterson Leif E, Ozen Mustafa, Greenberg Norman M, Ortega Sagrario, Basilico Claudio, Ittmann Michael
Department of Pathology, Baylor College of Medicine and Houston Department of Veterans Affairs Medical Center, Houston, Texas 77030, USA.
Cancer Res. 2003 Sep 15;63(18):5754-60.
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.
成纤维细胞生长因子（FGF）2（即碱性FGF）在人类前列腺癌中的表达水平升高。FGF2可促进细胞运动和增殖，增加肿瘤血管生成，并抑制细胞凋亡，所有这些在肿瘤进展中都起着重要作用。为了确定FGF2在前列腺癌进展中是否起关键作用，我们使用了小鼠前列腺转基因腺癌（TRAMP）模型系统。高比例的TRAMP小鼠会发生转移性前列腺癌，因此TRAMP模型可用于评估癌症进展。将TRAMP小鼠与FGF2基因敲除（FGF2(-/-)）小鼠杂交，并将FGF2等位基因失活的半合子或纯合子TRAMP小鼠的肿瘤进展与野生型TRAMP小鼠的进展进行比较。即使一个FGF2等位基因失活也会导致生存率提高、转移减少以及原发性前列腺肿瘤向低分化表型进展的抑制。与野生型小鼠相比，FGF(+/-)和FGF(-/-)小鼠中出现的低分化肿瘤表达更高水平的血管内皮生长因子，并且在某些情况下，酸性FGF细胞内结合蛋白（一种核FGF1结合蛋白）水平升高。这些发现表明，FGF2介导的血管生成和核内FGF2活性均可能促进肿瘤进展，并支持FGF2在体内前列腺癌进展中起重要作用这一假说。
