Overexpression of CEACAM6 promotes migration and invasion of oestrogen-deprived breast cancer cells.

Overexpression of CEACAM6 promotes migration and invasion of oestrogen-deprived breast cancer cells.
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DOI:
10.1016/j.ejca.2008.05.016
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发表时间:
2008-08
影响因子:
8.4
通讯作者:
Jordan, V. Craig
Jordan, V. Craig
中科院分区:
医学1区
文献类型:
--
作者:
Lewis-Wambi, Joan S.;Cunliffe, Heather E.;Kim, Helen R.;Willis, Amanda L.;Jordan, V. Craig

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癌胚抗原相关细胞粘附分子 6 (CEACAM6) 是一种细胞间粘附分子,在多种人类癌症中过度表达,包括结肠癌、乳腺癌和肺癌,与肿瘤发生、肿瘤细胞粘附、侵袭和转移相关。在本研究中,我们发现 CEACAM6 在一组雌激素受体 (ERα) 阳性人乳腺癌细胞系(MCF-7:5C 和 MCF-7:2A)中过度表达,这些细胞系已获得对雌激素剥夺的抵抗力,并且这种过度表达与体外更具侵袭性的侵袭表型相关。表达阵列分析显示,MCF-7:5C 和 MCF-7:2A 细胞过表达 CEACAM6 mRNA 分别是 27 倍和 12 倍,与表达低水平 CEACAM6 的非侵袭性野生型 MCF-7 细胞相比,侵袭性高 6 至 15 倍。使用小干扰 RNA (siRNA) 抑制 CEACAM6 表达可完全逆转 MCF-7:5C 和 MCF-7:2A 细胞的迁移和侵袭,并显着降低这些细胞中的 E-钙粘蛋白、Akt 和表达。总之,我们的研究结果表明 CEACAM6 是耐药雌​​激素剥夺乳腺癌细胞迁移和侵袭的独特介质,并表明该蛋白可能是转移的重要生物标志物。
Carcinocinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an intercellular adhesion molecule that is overexpressed in a wide variety of human cancers, including colon, breast, and lung and is associated with tumourigenesis, tumour cell adhesion, invasion, and metastasis. In the present study, we showed that CEACAM6 was overexpressed in a panel of oestrogen receptor (ERα)-positive human breast cancer cell lines (MCF-7:5C and MCF-7:2A) that have acquired resistance to oestrogen deprivation and this overexpression was associated with a more aggressive invasive phenotype in vitro. Expression array analysis revealed that MCF-7:5C and MCF-7:2A cells overexpressed CEACAM6 mRNA by 27-fold and 12-fold, respectively, and were 6 to 15-times more invasive compared to non-invasive wild-type MCF-7 cells which expressed low levels of CEACAM6. Suppression of CEACAM6 expression using small interfering RNA (siRNA) completely reversed migration and invasion of MCF-7:5C and MCF-7:2A cells and it significantly reduced E-cadherin, Akt, and expression in these cells. In conclusion, our findings establish CEACAM6 as a unique mediator of migration and invasion of drug resistant oestrogen deprived breast cancer cells and suggest that this protein could be an important biomarker of metastasis.
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