Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours.

Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours.
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人FRAT1表达的组织微阵列分析及其与β-catenin在卵巢肿瘤中的亚细胞定位的相关性。

DOI:
10.1038/sj.bjc.6602988
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发表时间:
2006-03-13
影响因子:
8.8
通讯作者:
Xu, N
Xu, N
中科院分区:
医学1区
文献类型:
--
作者:
Wang, Y;Hewitt, SM;Liu, S;Zhou, X;Zhu, H;Zhou, C;Zhang, G;Quan, L;Bai, J;Xu, N

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卵巢癌的发病机制尚不清楚,但有证据表明Wnt/β-catenin信号通路的异常激活在这种恶性肿瘤中起重要作用。然而,导致该途径活化的分子缺陷尚未阐明。在晚期T细胞淋巴瘤中经常重排的1(FRAT 1)是调节细胞质β-连环蛋白的候选者。在这项研究中,我们开发了原位杂交探针来评估FRAT 1的存在,并使用抗β-catenin抗体通过免疫组织化学来评估卵巢癌组织微阵列中β-catenin的表达水平和亚细胞定位。FRAT 1在正常卵巢组织和47%的卵巢腺癌中表达。共有46%的卵巢浆液性腺癌FRAT 1表达阳性。在55%的卵巢腺癌和59%的浆液性腺癌中观察到β-连环蛋白在细胞核和/或细胞质中的积聚。卵巢浆液性腺癌中FRAT 1与β-catenin的表达有显著相关性(P<0.01)。这些发现支持在卵巢浆液性腺癌中Wnt/β-catenin信号传导可能通过FRAT 1过表达而异常激活。FRAT 1在卵巢浆液性腺癌中过度表达的机制及其意义还有待进一步研究。
The mechanisms involved in the pathogenesis of ovarian cancer are poorly understood, but evidence suggests that aberrant activation of Wnt/β-catenin signalling pathway plays a significant role in this malignancy. However, the molecular defects that contribute to the activation of this pathway have not been elucidated. Frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) is a candidate for the regulation of cytoplasmic β-catenin. In this study, we developed in situ hybridisation probes to evaluate the presence of FRAT1 and used an anti-β-catenin antibody to evaluate by immunohistochemistry the expression levels and subcellular localisation of β-catenin in ovarian cancer tissue microarrays. Expression of FRAT1 was found in some human normal tissues and 47% of ovarian adenocarcinomas. A total of 46% of ovarian serous adenocarcinomas were positive for FRAT1 expression. Accumulation of β-catenin in the nucleus and/or cytoplasm was observed in 55% ovarian adenocarcinomas and in 59% of serous adenocarcinomas. A significant association was observed in ovarian serous adenocarcinomas between FRAT1 and β-catenin expression (P<0.01). These findings support that Wnt/β-catenin signalling may be aberrantly activated through FRAT1 overexpression in ovarian serous adenocarcinomas. The mechanism behind the overexpression of FRAT1 in ovarian serous adenocarcinomas and its significance is yet to be investigated.
DOI: 10.1177/106689690201000302
发表时间: 2002-07-01
影响因子: 1.2
作者:
Karbova, E;Davidson, B;Nesland, JM
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期刊: CANCER SCIENCE
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发表时间: 2002-01-18
影响因子: 4.8
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