Involvement of adenomatous polyposis coli (APC)/β-catenin signalling in human breast cancer
Involvement of adenomatous polyposis coli (APC)/β-catenin signalling in human breast cancer
复制标题
DOI：
10.1016/s0959-8049(99)00276-2
复制
发表时间：
2000-01-01
影响因子：
8.4
通讯作者：
Andersson, T
中科院分区：
文献类型：
--
作者：
Jönsson, M;Borg, Å;Andersson, T
我们通过分析 54 个原发性乳腺肿瘤（34 个导管肿瘤和 20 个小叶肿瘤）中 β-catenin 的表达，研究了腺瘤性结肠息肉病 (APC)/β-catenin 信号传导在乳腺癌发展中的相关性。我们发现 13% 的肿瘤在细胞质中表现出 β-连环蛋白水平上调，这表明 APC、β-连环蛋白信号传导成分的缺陷降低了 β-连环蛋白的降解率。 β-连环蛋白的氨基末端区域没有观察到突变，该区域包含对蛋白质的磷酸化依赖性降解很重要的保守丝氨酸残基，但 APC 蛋白在 6% 的肿瘤中发生了改变。仅在一个肿瘤中检测到β-连环蛋白的酪氨酸磷酸化，因此可能不是观察到的该蛋白质水平增加的原因。尽管 9% 的肿瘤表现出 c-MYC 蛋白上调，但与 β-catenin 过度表达没有相关性。这表明β-连环蛋白表达增加并不是乳腺癌中c-myc 基因激活的主要原因。必须确定选择性驱动乳腺癌中β-连环蛋白致癌活性的元素。 (C) 2000 Elsevier Science Ltd. 保留所有权利。
We studied the relevance of adenomatous polyposis coli (APC)/beta-catenin signalling in the development of breast cancer by analysing the expression of beta-catenin in 54 primary breast tumours (34 ductal and 20 lobular). We showed that 13% of the tumours exhibited upregulated levels of beta-catenin in the cytosol suggesting that defects in APC, beta-catenin signalling components had lowered the rate of beta-catenin degradation. No mutations were observed in the amino-terminal region of beta-catenin which comprises conserved serine residues important for phosphorylation-dependent degradation of the protein, but the APC protein was altered in 6% of the tumours. Tyrosine phosphorylation of beta-catenin was detected in only one tumour and could, therefore not have been responsible for the observed increased levels of this protein. Although 9% of the tumours displayed upregulation of c-MYC protein, there was no correlation with beta-catenin overexpression. suggesting that increased beta-catenin expression is not the major cause of c-myc gene activation in breast cancer. It is imperative that elements that selectively drive the oncogenic activity of beta-catenin in breast cancer be identified. (C) 2000 Elsevier Science Ltd. All rights reserved.