Fibroblast growth factor-10 - A second candidate stromal to epithelial cell andromedin in prostate
Fibroblast growth factor-10 - A second candidate stromal to epithelial cell andromedin in prostate
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DOI：
10.1074/jbc.274.18.12827
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发表时间：
1999-04-30
影响因子：
4.8
通讯作者：
McKeehan, WL
中科院分区：
文献类型：
--
作者：
Lu, WQ;Luo, YD;McKeehan, WL
成纤维细胞生长因子（FGF）-10是FGF-7的同源物，在正常大鼠前列腺组织、具有上皮和基质区室的分化良好的大鼠前列腺肿瘤中显著表达，并且仅在培养的衍生前列腺基质细胞中表达。与FGF-7相似，重组大鼠FGF-10是前列腺上皮细胞的特异性促分裂剂。与在组织中基质细胞中广泛表达的FGF-7相反，FGF-10的表达与肌肉来源的基质细胞的存在相关。放射性受体结合测定和共价交联分析显示，FGF-10以与FGF-7相同的亲和力结合至固有上皮细胞受体FGFR 2 IIIb，但与FGF-7不同的是，FGF-10还结合FGFR 1的IIIb剪接变体。RNA酶保护的mRNA表达分析显示，类似于FGF-7，FGF-10的表达对正常前列腺和非恶性分化肿瘤间质细胞中的雄激素有反应。虽然FGF-10 cDNA显示出分泌的信号序列，但培养的基质细胞显示出严格的细胞相关FGF-10抗原，其与交替翻译的细胞内同种型相关，FGF-10需要比FGF-7高1.4倍的NaCl从固定化肝素洗脱，并且结合到上皮细胞的细胞周基质上的位点数的四倍。结果表明，前列腺基质细胞衍生的FGF-10，像FGF-7一样，表现出雄激素调节肽的性质，其可能间接介导雄激素对上皮细胞生长和功能的控制，尽管FGF-10和FGF-7结合并激活相同的固有上皮细胞受体（FGFR 2 IIIb），细胞来源类型的差异，通过交替翻译的区室化，对FGFR 1 IIIb的亲和力，通过与细胞周围基质硫酸乙酰肝素的差异相互作用而获得FGFR，表明它们可能在前列腺稳态中发挥独立和代偿作用。
Fibroblast growth factor (FGF)-10, a homologue of FGF-7, is expressed significantly in normal rat prostate tissue, well differentiated rat prostate tumors with an epithelial and stromal compartment and only in derived prostate stromal cells in culture. Similar to FGF-7, recombinant rat FGF-10 was a specific mitogen for prostate epithelial cells. In contrast to FGF-7 which is widely expressed among stromal cells in tissues, the expression of FGF-10 correlated with the presence of stromal cells of muscle origin. Radioreceptor binding assays and covalent cross-linking analysis revealed that FGF-10 binds with an affinity equal to FGF-7 to resident epithelial cell receptor, FGFR2IIIb, but unlike FGF-7 also binds the IIIb splice variant of FGFR1. Analysis of mRNA expression by RNase protection revealed that, similar to FGF-7, the expression of FGF-10 was responsive to androgen in stromal cells from normal prostate and nonmalignant differentiated tumors. Although FGF-10 cDNA exhibits a signal sequence for secretion, cultured stromal cells exhibit strictly a cell-associated FGF-10 antigen that correlates with an alternately translated intracellular isoform, FGF-10 requires 1.4 times higher NaCl for elution from immobilized heparin than does FGF-7 and binds to four times the number of sites on the pericellular matrix of epithelial cells. The results show that prostate stromal cell-derived FGF-10, like FGF-7, exhibits the properties of an andromedin which may indirectly mediate control of epithelial cell growth and function by androgen, Although FGF-10 and FGF-7 bind and activate the same resident epithelial cell receptor (FGFR2IIIb), differences in cell type of origin, compartmentation by alternate translation, the affinity for FGFR1IIIb, and access to FGFR by differential interaction with pericellular matrix heparan sulfate suggest they may play both independent and compensatory roles in prostate homeostasis.