Roghani Monireh, Moscatelli David
Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
Prostate. 2007 Feb 1;67(2):115-24. doi: 10.1002/pros.20448.
Fibroblast growth factor receptor 1 (FGFR1) mRNA can be alternatively spliced to generate isoforms containing (FGFR1alpha) or lacking (FGFR1beta) the first immunoglobulin-like domain. We examined which isoforms are expressed by cultured prostate cells, their affinities for FGF-2, and the effect of heparin on FGF-2 binding.
FGFR1 isoform expression was examined by RT-PCR. FGFR1alpha and FGFR1beta were expressed in CHO cells mutant in heparan sulfate synthesis, and their affinities for FGF-2, FGF-1, FGF-4, and FGF-6 were determined in the presence and absence of heparin.
FGFR1alpha was expressed in luminal epithelial cells, whereas FGFR1beta was expressed in basal epithelial and smooth muscle cells. FGFR1beta bound FGF-2 with three-fourfold higher affinity than FGFR1alpha both in the presence and absence of heparin. Heparin increased affinity of both receptor isoforms for FGF-2 approximately four-fivefold.
Prostate smooth muscle and basal epithelial cells are likely to be more sensitive than luminal epithelial cells to the low concentrations of FGFs present in vivo.
成纤维细胞生长因子受体1(FGFR1)信使核糖核酸(mRNA)可通过可变剪接产生包含第一个免疫球蛋白样结构域的异构体(FGFR1α)或缺乏该结构域的异构体(FGFR1β)。我们研究了培养的前列腺细胞表达哪些异构体,它们对FGF-2的亲和力,以及肝素对FGF-2结合的影响。
通过逆转录聚合酶链反应(RT-PCR)检测FGFR1异构体的表达。FGFR1α和FGFR1β在硫酸乙酰肝素合成缺陷的中国仓鼠卵巢(CHO)细胞中表达,并在有和没有肝素的情况下测定它们对FGF-2、FGF-1、FGF-4和FGF-6的亲和力。
FGFR1α在腔上皮细胞中表达,而FGFR1β在基底上皮细胞和平滑肌细胞中表达。在有和没有肝素的情况下,FGFR1β对FGF-2的结合亲和力均比FGFR1α高3至4倍。肝素使两种受体异构体对FGF-2的亲和力增加约4至5倍。
前列腺平滑肌细胞和基底上皮细胞可能比腔上皮细胞对体内存在的低浓度成纤维细胞生长因子(FGFs)更敏感。