Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines
Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines
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DOI：
10.1530/eje.0.1500173
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发表时间：
2004-02-01
影响因子：
5.8
通讯作者：
Muccioli, G
中科院分区：
文献类型：
--
作者：
Cassoni, P;Ghé, C;Muccioli, G
背景资料：Ghrelin是一种天然的生长激素促分泌素（GHS），在前列腺癌细胞系中被发现。目的：研究Ghrelin及其受体在前列腺癌细胞系DU-145、PC-3和LNCaP中的存在，并评估Ghrelin及其循环形式去辛酰Ghrelin对细胞增殖的影响。采用RT-PCR、原位杂交、免疫组织化学和酶免疫分析等方法对组织、细胞系和培养液中Ghrelin、1a型和1b型GHS受体（GHS-R）的mRNA和蛋白水平进行检测。通过放射受体测定法测定Ghrelin结合。结果：Ghrelin mRNA在前列腺癌和前列腺增生组织中表达，免疫组化染色为阴性。GHS-R1 a和1b mRNA在癌中缺失，但GHS-R1 b mRNA在50%的增生中存在。Ghrelin肽和mRNA仅在PC-3细胞中表达，而GHS-R1 a和1b mRNA仅在DU-145细胞中表达。在前列腺肿瘤、DU-145和PC-3细胞膜中检测到特异性[I-125]Tyr（4）-ghrelin结合，该结合被ghrelin、合成GHS和去辛酰基ghrelin（缺乏GHS-R1 a结合亲和力和GH释放活性）取代。Ghrelin和des-acyl ghrelin抑制DU-145细胞增殖，在PC-3细胞中显示双相效应，在LNCaP细胞中无效。结论：在人前列腺肿瘤中存在GHS R1 a和1b以外的特异性GHS结合位点。在前列腺癌细胞系中，除去酰基ghrelin外，Ghrelin对细胞增殖具有不同的作用。
Background: Ghrelin, a natural growth hormone secretagogue (GHS), has been identified in prostate carcinoma cell lines.Objectives: To investigate the presence of ghrelin and its receptors in human prostate tumours and in DU-145, PC-3 and LNCaP prostate carcinoma cell lines, and to assesss the effects of ghrelin and its more abundant circulating form, des-octanoyl ghrelin, on cell proliferation.Methods: Ghrelin and types la and 1b GHS receptor (GHS-R) were determined at the mRNA and protein levels by RT-PCR, in situ hybridization, immunohistochemistry and enzyme immunoassay in tissues, cell lines and culture medium. Ghrelin binding was determined by radioreceptor assay. The effects on cell proliferation were evaluated by growth curves.Results: Ghrelin mRNA was found in prostatic carcinomas and benign hyperplasias, but immunohistochemistry was negative. GHS-R1a and 1b mRNAs were absent from carcinomas, but GHS-R1b mRNA was present in 50% of hyperplasias. Ghrelin peptide and mRNA were present in PC-3 cells exclusively, whereas GHS-R1a and 1b mRNAs were expressed in DU-145 cells only. Specific [I-125]Tyr(4)-ghrelin binding was detected in prostate tumour, DU-145 and PC-3 cell membranes and the binding was displaced by ghrelin, synthetic GHS and des-octanoyl ghrelin, which is devoid of GHS-R1a binding affinity and GH-releasing activity. Ghrelin and des-acyl ghrelin inhibited DU-145 cell proliferation, displayed a biphasic effect in PC-3 cells and were ineffective in LNCaP cells.Conclusions: Specific GHS binding sites, other than GHS-R1a and 1b, are present in human prostatic neoplasms. Ghrelin, in addition to des-acyl ghrelin, exerts different effects on cell proliferation in prostate carcinoma cell lines.