Over expression of Id-1 in prostate cancer

Over expression of Id-1 in prostate cancer
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DOI:
10.1016/s0022-5347(05)65044-6
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发表时间:
2002-06-01
期刊:
影响因子:
6.6
通讯作者:
Wong, YC
Wong, YC
中科院分区:
医学1区
文献类型:
--
作者:
Ouyang, XS;Wang, X;Wong, YC

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用途:螺旋-环-螺旋蛋白Id-1用于阻止碱性螺旋-环-螺旋转录因子与DNA结合,从而抑制分化相关基因的转录。Id-1在某些肿瘤如乳腺癌、食管癌、胰腺癌和甲状腺髓样癌中过表达。在Noble大鼠中,我们先前已经证明Id-1的上调与性激素诱导的前列腺癌的发展密切相关。因此,我们推测Id-1的过度表达也会发生在人前列腺癌中,Id-1蛋白可能作为前列腺癌发生的潜在标志物。为了验证这一假设,我们分析了Id-1信使RNA和蛋白表达的原位杂交和免疫组化研究在人类正常前列腺,良性前列腺增生(BPH)和前列腺癌tissues.Materials和方法:病理标本,从19例BPH和47例前列腺癌,代表了一个完整的范围Gleason分级。共12例正常前列腺组织标本用于比较。结果:Id-1蛋白在正常前列腺和BPH组织中均呈阴性或弱阳性表达,而在正常前列腺和BPH组织中均呈阴性或弱阳性表达。相反,所有前列腺癌活检显示肿瘤细胞在信使RNA和蛋白质水平上的Id-1表达显著阳性。此外,Id-1在低分化癌中的表达强于高分化癌,表明Id-1的表达水平可能与肿瘤的恶性程度有关。结论:我们的结果表明Id-1的过度表达可能在前列腺癌的发生发展中发挥重要作用。Id-1蛋白作为前列腺癌标志物的潜在用途应进一步探索。
Purpose: The helix-loop-helix protein Id-1 serves to prevent basic helix-loop-helix transcription factors from binding to DNA, thus, inhibiting the transcription of differentiation associated genes. Over expression of Id-1 has been reported in certain tumors, such as breast, esophageal, pancreatic and medullary thyroid cancers. In Noble rats we have previously demonstrated that up-regulation of Id-1 is closely associated with the development of sex hormone induced prostate cancers. Therefore, we hypothesized that over expression of Id-1 would also occur in human prostate cancer and Id-1 protein may serve as a potential marker for prostate carcinogenesis. To test this hypothesis we analyzed Id-1 messenger RNA and protein expression by in situ hybridization and immunohistochemical study in human normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer tissues.Materials and Methods: Pathological specimens were obtained from 19 patients with BPH and 47 with prostate carcinoma, representing a complete range of Gleason grades. A total of 12 normal prostate tissue specimens were used for comparison. Immunohistochemical study was performed using the polyclonal antibody against human Id-1 protein and an RNA probe was generated from Id-1 complementary DNA for in situ hybridization.Results: Negative to weak expression of Id-1 in normal prostate or BPH tissue was observed on immunohistochemical study and in situ hybridization. In contrast, all prostate cancer biopsies showed significant positive Id-1 expression in tumor cells at the messenger RNA and protein levels. Furthermore, Id-1 expression was stronger in poorly differentiated than in well differentiated carcinomas, suggesting that the level of Id-1 expression may be associated with tumor malignancy.Conclusions: Our results suggest that over expression of Id-1 may have important roles in the development of prostate cancer. The potential use of Id-1 protein as a marker for prostate cancer should be further explored.