INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND ITS BINDING-PROTEIN IGFBP-4 IN HUMAN PROSTATIC HYPERPLASTIC TISSUE - GENE-EXPRESSION AND ITS CELLULAR-LOCALIZATION
INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND ITS BINDING-PROTEIN IGFBP-4 IN HUMAN PROSTATIC HYPERPLASTIC TISSUE - GENE-EXPRESSION AND ITS CELLULAR-LOCALIZATION
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DOI：
10.1210/jc.78.3.778
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发表时间：
1994-03-01
影响因子：
5.8
通讯作者：
FIORELLI, G
中科院分区：
文献类型：
--
作者：
BARNI, T;VANNELLI, BG;FIORELLI, G
已有研究报道：1)I型胰岛素样生长因子(IGF)受体存在于人前列腺组织中；2)IGF-I受体主要定位于上皮细胞；3)IGF-I是培养中的前列腺上皮细胞的有丝分裂原；4)这些细胞在条件培养液中释放IGF结合蛋白(IGFBPs)。为了进一步了解IGF-I在人前列腺中的作用机制，我们研究了编码IGF-I和IGFBP-4的mRNA在人前列腺增生症(BPH)组织中的表达和细胞定位。用包含IGF-I和IGFBP-4全部编码区的cDNA探针对从BPH组织中提取的总RNA进行Northern分析，发现存在多个长度分别为7.5、1.7、1.3和1.1kb的IGF-I mRNA转录本和一个2.1kb的IGFBP-4转录本。与Northern杂交结果表明，IGFBP-4mRNA主要在间质细胞中表达，而IGFBP-4mRNA主要在上皮细胞中表达。此外，还检测了酸化和反相色谱后BPH组织提取液中免疫活性IGF-I的含量。6例BPH组织中(+/-SD)IGF-I的平均含量为28.1+/-4.0 ng/g组织，提示在人前列腺中，局部分泌的IGF-I以旁分泌的方式发挥其主要的生物学效应，IGFBP-4主要由IGF-I靶细胞表达。
It has been previously reported that 1) type I insulin-like growth factor (IGF) receptors are present in the human prostatic tissue; 2) IGF-I receptors are mainly localized in the epithelial cells; 3) IGF-I is a mitogen for prostatic epithelial cells in culture; and 4) IGF-binding proteins (IGFBPs) are released by these cells in the conditioned medium. To add information on the mechanism of IGF-I action in the human prostate, we studied the expression and cellular localization of mRNA encoding IGF-I and IGFBP-4 in human prostatic hyperplastic (BPH) tissue. Northern analysis of total RNA extracted from BPH tissues with cDNA probes containing the entire coding regions for IGF-I and IGFBP-4 documented the presence of multiple IGF-I mRNA transcripts with lengths of 7.5, 1.7, 1.3, and 1.1 kilobases and a single 2.1-kilobase transcript of IGFBP-4 mRNA. In situ hybridization with the cDNA probes used for Northern analysis and with cRNA probes synthesized from the respective cDNA demonstrated that IGF-I mRNA was only localized in the stromal cells, whereas IGFBP-4 mRNA was predominantly expressed by epithelial cells. In addition, immunoreactive IGF-I was measured in BPH tissue extracts after acidification and reverse phase chromatography. The mean (+/-SD) IGF-I content of six BPH tissues was 28.1 +/- 4.0 ng/g tissue.Our results suggest that in the human prostate, the locally secreted IGF-I exerts its principal biological effects with a paracrine mode of action and demonstrate that IGFBP-4 is mainly expressed by IGF-I target cells.