Carstens R P, Eaton J V, Krigman H R, Walther P J, Garcia-Blanco M A
Department of Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
Oncogene. 1997 Dec 18;15(25):3059-65. doi: 10.1038/sj.onc.1201498.
Progression of prostate cancer from an androgen sensitive to androgen insensitive tumor has previously been shown to be accompanied by a change in alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) in a rat model of prostate cancer. This change results in loss of the FGF-R2(IIIb) isoform and predominant expression of the FGF-R2(IIIc) isoform. We sought to determine whether this change in FGF-R2 splicing is also associated with androgen insensitivity in human prostate tumors. We analysed three well characterized human prostate cancer cell lines and three metastatic prostate tumors which have been maintained as xenografts in nude mice. One of the cell lines, LNCaP, and two of the xenografts, DUKAP-1 and DUKAP-2, have been characterized as androgen sensitive, whereas two of the cell lines, DU-145 and PC-3, and one of the xenografts, DU9479, display androgen independent growth. Using an RT-PCR based assay, we demonstrated that progressive loss of the FGF-R2(111b) isoform correlated with androgen insensitivity in these human prostate cancer models. These findings lend support to the hypothesis that that loss of FGF-R2(IIIb) may be one step in a series of events which lead to progression of human prostate cancer.
在前列腺癌大鼠模型中，先前已表明前列腺癌从雄激素敏感肿瘤发展为雄激素不敏感肿瘤的过程伴随着成纤维细胞生长因子受体2（FGF-R2）可变剪接的变化。这种变化导致FGF-R2（IIIb）亚型的缺失和FGF-R2（IIIc）亚型的主要表达。我们试图确定FGF-R2剪接的这种变化是否也与人类前列腺肿瘤中的雄激素不敏感性有关。我们分析了三种特征明确的人类前列腺癌细胞系和三种已在裸鼠中作为异种移植维持的转移性前列腺肿瘤。其中一种细胞系LNCaP以及两种异种移植DUKAP-1和DUKAP-2已被表征为雄激素敏感，而两种细胞系DU-145和PC-3以及一种异种移植DU9479显示出雄激素非依赖性生长。使用基于RT-PCR的检测方法，我们证明在这些人类前列腺癌模型中，FGF-R2（111b）亚型的逐渐丧失与雄激素不敏感性相关。这些发现支持了这样的假设，即FGF-R2（IIIb）的丧失可能是导致人类前列腺癌进展的一系列事件中的一个步骤。
