Up-regulation of TRPM-2, MMP-7 and ID-1 during sex hormone-induced prostate carcinogenesis in the Noble rat
Up-regulation of TRPM-2, MMP-7 and ID-1 during sex hormone-induced prostate carcinogenesis in the Noble rat
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DOI：
10.1093/carcin/22.6.965
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发表时间：
2001-06-01
期刊：
影响因子：
4.7
通讯作者：
Wong, YC
中科院分区：
文献类型：
--
作者：
Ouyang, XS;Wang, X;Wong, YC
前列腺癌是西方世界最常诊断的恶性肿瘤，睾酮和雌激素比例随着年龄的增长而变化是这种疾病发展的潜在危险因素之一。然而，与前列腺癌发生中激素失衡相关的分子机制知之甚少。在这项研究中，我们使用睾酮和雌二醇-17 β的组合在Noble大鼠中诱导前列腺增生、异型增生和腺癌的高发病率。使用这个动物模型，我们研究了基因表达谱在性行为诱导的前列腺癌的发生过程中，使用cDNA阵列技术，结果进一步证实了RT-PCR，蛋白质印迹和免疫组化分析。我们发现TRPM-2（睾酮抑制的前列腺信息-2），MMP-7（基质金属蛋白酶-7）和Id-1（分化或DNA结合抑制剂）在性激素诱导的前列腺癌的发展过程中上调。TRPM-2和MMP-7的表达增加，观察到在癌前病变和恶性组织性激素治疗后，表明它们的作用，在激素反应和前列腺癌的发展的早期阶段。与此相反，Id-1在所有癌前病变中表达水平相对较低，但在恶性细胞中表达增加，这表明其作为前列腺癌细胞生物标志物的潜在作用。此外，Id-1的表达在低分化病变中似乎比在高分化癌中更强，这表明Id-1的表达水平可能与肿瘤的恶性程度相关。我们的研究结果提供了TRPM-2，MMP-7和Id-1在性生活诱导的前列腺癌发生过程中上调的第一个证据，并强烈建议他们与前列腺癌的发展。
Prostate cancer is the most frequently diagnosed malignancy in the Western world and changes in the ratio of testosterone and estrogens with advancing age is one of the potential risk factors in the development of this disease. However, the molecular mechanisms associated with hormone imbalance in prostate carcinogenesis are poorly understood. In this study we induced a high incidence of prostate hyperplasia, dysplasia and adenocarcinoma in the Noble rat using a combination of testosterone and estradiol-17 beta. Using this animal model, we studied the gene expression profile during sex hormone-induced prostate carcinogenesis using a cDNA array technique; the results were further confirmed by RT-PCR, western blotting and immunohistochemical analyses. We found up-regulation of TRPM-2 (testosterone-repressed prostatic message-2), MMP-7 (matrix metalloproteinase-7) and Id-1 (inhibitor of differentiation or DNA binding) during development of sex hormone-induced prostate cancer. Increased expression of TRPM-2 and MMP-7 was observed in both premalignant and malignant tissues after sex hormone treatment, indicating their role in the early stages of hormone response and prostate cancer development. In contrast, Id-1 was expressed at relatively low levels in all premalignant samples but increased in malignant cells, suggesting its potential roles as a biomarker for prostate cancer cells, Furthermore, expression of Id-1 appeared to be stronger in poorly differentiated lesions than in well-differentiated carcinomas, suggesting that the levels of Id-1 expression may be correlated with the malignancy of tumors. Our results provide the first evidence of up-regulation of TRPM-2, MMP-7 and Id-1 during sex hormone-induced prostate carcinogenesis and strongly suggest their association with the development of prostate cancer.