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人肾细胞癌中上皮钙通道 TRPV5 和 TRPV6 的表达减少与维生素 D 受体有关。

Decreased expression of the epithelial Ca2+ channel TRPV5 and TRPV6 in human renal cell carcinoma associated with vitamin D receptor.

机构信息

Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.

出版信息

J Urol. 2011 Dec;186(6):2419-25. doi: 10.1016/j.juro.2011.07.086. Epub 2011 Oct 21.

DOI:10.1016/j.juro.2011.07.086
PMID:22019165
Abstract

PURPOSE

We investigated the expression of epithelial Ca(2+) channel TRPV (transient receptor potential vanilloid subfamily) 5 and 6, and vitamin D receptor in primary human renal cell carcinoma and benign peritumor tissues, and assessed the possible association between TRPV5/6 and vitamin D receptor expression.

MATERIALS AND METHODS

Fresh-frozen primary tumor and peritumor tissues from 27 patients diagnosed with renal cell carcinoma were analyzed for TRPV5/6 and vitamin D receptor expression by quantitative reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry.

RESULTS

Quantitative reverse transcriptase-polymerase chain reaction revealed that TRPV5/6 and vitamin D receptor expression was decreased 38.11, 4.44 and 3.20 times in renal cell carcinoma vs normal kidney tissue (p = 0.012, 0.002 and 0.020, respectively). Relatively higher expression was noted for chromophobe renal cell carcinoma than for the other renal cell carcinoma subtypes. Vitamin D receptor mRNA expression significantly correlated with that of TRPV6 (r = 0.508, p = 0.007) and TRPV5 (r = 0.697, p = 0.032) in renal cell carcinoma. Western blot showed results similar to those of reverse transcriptase-polymerase chain reaction. Different expression was detected between kidney and renal cell carcinoma tissue. Immunohistochemical analysis verified strong detection of TRPV5/6 and vitamin D receptor in distal nephrons but demonstrated weak or no immunostaining much more often in renal cell carcinoma.

CONCLUSIONS

Decreased TRPV5/V6 expression was noted in renal cell carcinoma, which correlated with vitamin D receptor. Different expression was also detected among the different renal cell carcinoma histopathological subtypes. Our observations suggest that altered vitamin D receptor expression may be associated with renal cell carcinoma carcinogenesis via TRPV5/6.

摘要

目的

我们研究了上皮钙通道 TRPV(瞬时受体电位香草酸亚型)5 和 6 以及维生素 D 受体在原发性人肾细胞癌和良性肿瘤周围组织中的表达,并评估了 TRPV5/6 和维生素 D 受体表达之间的可能关联。

材料和方法

通过定量逆转录聚合酶链反应、Western blot 和免疫组织化学分析 27 例诊断为肾细胞癌的患者的新鲜冷冻原发性肿瘤和肿瘤周围组织中 TRPV5/6 和维生素 D 受体的表达。

结果

定量逆转录聚合酶链反应显示,与正常肾组织相比,肾细胞癌中 TRPV5/6 和维生素 D 受体的表达分别降低了 38.11、4.44 和 3.20 倍(p = 0.012、0.002 和 0.020)。嗜铬细胞瘤肾细胞癌的相对表达较高。维生素 D 受体 mRNA 表达与肾细胞癌中 TRPV6(r = 0.508,p = 0.007)和 TRPV5(r = 0.697,p = 0.032)的表达显著相关。Western blot 显示与逆转录聚合酶链反应相似的结果。在肾组织和肾细胞癌组织之间检测到不同的表达。免疫组织化学分析证实 TRPV5/6 和维生素 D 受体在远曲小管中强烈表达,但在肾细胞癌中更常表现为弱表达或无表达。

结论

肾细胞癌中 TRPV5/V6 表达降低,与维生素 D 受体相关。不同的表达也在不同的肾细胞癌组织病理学亚型中检测到。我们的观察结果表明,维生素 D 受体表达的改变可能通过 TRPV5/6 与肾细胞癌的发生有关。

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