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人端粒酶催化亚基hTERT在人乳腺组织中的表达与分布

Expression and distribution of human telomerase catalytic component, hTERT, in human breast tissues.

作者信息

Yano Yasuo, Yoshida Kazuhiro, Osaki Akihiko, Toge Tetsuya, Tahara Hidetoshi, Ide Toshinori, Yasui Wataru

机构信息

Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.

出版信息

Anticancer Res. 2002 Nov-Dec;22(6C):4101-7.

Abstract

BACKGROUND

Activation of telomerase is essential in a variety of malignant tumors. However, the regulation of its activation and the expression of human telomerase reverse transcriptase (hTERT) are not fully understood in breast tissues.

MATERIALS AND METHODS

In order to clarify this point, the telomerase activity was examined by telomeric repeat amplification protocol (TRAP) assay and quantified by hybridization protection assay (HPA) and, moreover, the expressions of hTERT mRNA and protein were examined by RT-PCR and immunohistochemistry, respectively.

RESULTS

Telomerase activity and the expression of hTERT mRNA were detected in 41(75%) and 37(67%) cases among 55 breast carcinomas, respectively. However, the telomerase ZV activity was detected in only 14(40%) among 35 benign breast tumors. Strong correlation was observed between telomerase activity and hTERT mRNA expression, as described previously. Moreover, the strong expression of hTERT protein in the nucleus of the cell was detected in 30 (57%) cases among 53 breast carcinomas and weak expression of the protein was also detected in 11 (35%) cases among 31 benign breast tumors by immunohistochemistry. There were 12 breast carcinomas which had no telomerase activity. Three of them had hTERT mRNA and protein and in 3 other cases, only hTERT protein was detected. Five cases had the expression of mRNA but not the protein and it was only one case which had no activity and expression of hTERT mRNA and protein. However, in benign tumors, 14 (87.5%) cases among 16 TRAP-negative tumors had no mRNA and protein expression.

CONCLUSION

These results indicate that complicated regulation might be involved in the regulation of telomerase activity and also the activation of the gene may be important in the carcinogenesis of human breast carcinomas.

摘要

背景

端粒酶的激活在多种恶性肿瘤中至关重要。然而,在乳腺组织中,其激活调控以及人端粒酶逆转录酶(hTERT)的表达尚未完全明确。

材料与方法

为阐明这一点,采用端粒重复序列扩增法(TRAP)检测端粒酶活性,并通过杂交保护分析法(HPA)进行定量,此外,分别采用逆转录聚合酶链反应(RT-PCR)和免疫组织化学法检测hTERT mRNA和蛋白的表达。

结果

55例乳腺癌中,分别有41例(75%)和37例(67%)检测到端粒酶活性和hTERT mRNA表达。然而,35例乳腺良性肿瘤中仅14例(40%)检测到端粒酶ZV活性。如前所述,端粒酶活性与hTERT mRNA表达之间存在强相关性。此外,免疫组织化学法检测发现,53例乳腺癌中有30例(57%)细胞胞核中hTERT蛋白呈强表达,31例乳腺良性肿瘤中有11例(35%)蛋白呈弱表达。有12例乳腺癌未检测到端粒酶活性。其中3例有hTERT mRNA和蛋白,另外3例仅检测到hTERT蛋白。5例有mRNA表达但无蛋白表达,仅1例无hTERT mRNA和蛋白活性及表达。然而,在良性肿瘤中,16例TRAP阴性肿瘤中有14例(87.5%)无mRNA和蛋白表达。

结论

这些结果表明,端粒酶活性的调控可能涉及复杂机制,而且该基因的激活在人类乳腺癌的发生中可能很重要。

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