APC truncation and increased β-catenin levels in a human breast cancer cell line

APC truncation and increased β-catenin levels in a human breast cancer cell line
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DOI:
10.1093/carcin/21.7.1453
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发表时间:
2000-07-01
期刊:
影响因子:
4.7
通讯作者:
Kitajewski, J
Kitajewski, J
中科院分区:
医学2区
文献类型:
--
作者:
Schlosshauer, PW;Brown, SA;Kitajewski, J

文献摘要

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腺瘤性结肠息肉病 (APC) 肿瘤抑制基因或 β-连环蛋白基因的突变存在于大多数结肠癌中,而在其他肿瘤类型中则较少见。在这项研究中,我们通过蛋白质印迹、蛋白质截短测定和 DNA 序列分析,筛选了 24 个人类乳腺癌细胞系和三个永生化人类乳腺上皮细胞系的 β- 和 γ-连环蛋白以及 APC 的变化。在一种细胞系 (DU 4475) 中,鉴定出 APC 突变 (E1577stop),导致表达截短的 APC。这种突变与胞质 γ-连环蛋白水平升高有关,可能是由于 APC 功能丧失所致,如结肠癌。在β-或γ-连环蛋白基因的外显子3中未发现突变,我们得出结论,APC突变和β-连环蛋白上调可能在人类乳腺癌细胞中以低频率发生。
Mutations in the Adenomatous Polyposis Coli (APC) tumor suppressor gene or the beta-catenin gene are present in most colon cancers and less frequently in other tumor types. In this study, we screened 24 human breast cancer cell lines and three immortalized human breast epithelial cell lines for alterations in beta- and gamma-catenin and APC by western blotting, protein truncation assay and DNA sequence analysis. In one cell line (DU 4475), an APC mutation was identified (E1577stop) that resulted in expression of truncated APC. This mutation was associated with elevated cytosolic gamma-catenin levels, probably due to loss of APC function, as in colon cancers. No mutations were found in exon 3 of the beta- or gamma-catenin genes, We conclude that APC mutations and beta-catenin upregulation may occur with low frequency in human breast cancer cells.