在一項(xiàng)新研究中,，給一個(gè)癌基因加上一種分子“便利貼(post-it note)”能夠預(yù)測(cè)患者乳腺癌擴(kuò)散的風(fēng)險(xiǎn),。
來(lái)自英國(guó)倫敦帝國(guó)學(xué)院(Imperial College London)的英國(guó)癌癥研究中心研究人員證實(shí)CACNA2D3基因上高水平的被稱作甲基化的分子修飾與乳腺癌患者體內(nèi)這種疾病的擴(kuò)散相關(guān)聯(lián),。2012年7月10日,，相關(guān)研究成果發(fā)表在British Journal of Cancer期刊上,。
已知基因CACNA2D3是一個(gè)阻止癌癥產(chǎn)生的腫瘤抑制基因,。在健康的乳腺細(xì)胞中,，它并未甲基化,，但是在乳腺癌細(xì)胞中，它是高度甲基化的,。甲基化是一種常見(jiàn)的細(xì)胞過(guò)程：將甲基加到DNA上以便阻止基因表達(dá),，即在DNA上就像便利貼那樣告訴細(xì)胞何時(shí)關(guān)閉基因表達(dá)。
這項(xiàng)研究揭示加入甲基基團(tuán)到CACNA2D3基因上將阻止它發(fā)揮抵抗癌癥產(chǎn)生的作用,。已知這個(gè)基因在諸如肺癌,、腎細(xì)胞癌、神經(jīng)母細(xì)胞瘤(neuroblastoma)和骨肉瘤(osteosarcoma)之類(lèi)的多種癌癥中存在缺陷或缺失,，但是這項(xiàng)研究是首次將它與乳腺癌關(guān)聯(lián)在一起,。
論文第一作者Carlo Palmieri博士說(shuō)，“我們的研究提示著甲基基團(tuán)能夠抑制CACNA2D3基因傳遞的信息：阻斷它抵抗乳腺癌的潛在保護(hù)性作用,。這個(gè)基因的甲基化可能能夠被用來(lái)預(yù)測(cè)哪些乳腺癌患者有更大的可能性發(fā)生癌癥擴(kuò)散,，從而有助于醫(yī)生們決定哪些治療策略將是最為效果的。”
下一階段將是在更大的研究中重復(fù)這些發(fā)現(xiàn)以便證實(shí)分析這個(gè)基因的甲基化是否是一種有效的測(cè)試,。(生物谷：Bioon.com)
本文編譯自'Post-it note' on breast cancer gene signals risk of disease spreading
doi:10.1038/bjc.2012.231
PMC:
PMID:
Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas
C Palmieri, B Rudraraju, M Monteverde, L Lattanzio, O Gojis, R Brizio, O Garrone, M Merlano, N Syed, C Lo Nigro and T Crook
Background: Calcium is an important intracellular messenger that mediates many biological processes that are relevant to the malignant process. Calcium ion channels are key in controlling the intracellular calcium, and little is known about their role in human cancer. Methods: We used qPCR and pyrosequencing to investigate expression and epigenetic regulation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) in breast cancer cell lines, primary cancers and metastatic lesions. Results: Expression of CACNA2D3 mRNA is regulated in breast cancer cell lines by methylation in the CpG island located in the 5′ regulatory region of the gene. Expression is upregulated by azacytidine (AZA) in cells with CpG island methylation but unaffected in cells lacking methylation. In primary breast carcinomas, methylation is more common in cancers, which subsequently relapse with loco-regional and, particularly, visceral metastatic disease in both oestrogen receptor-α (ER)-positive and -negative cases. Furthermore, CACNA2D3 CpG island is frequently methylated in breast cancer that has metastasised to the central nervous system. Conclusion: Methylation-dependent transcriptional silencing of CACNA2D3 may contribute to the metastatic phenotype of breast cancer. Analysis of methylation in the CACNA2D3 CpG island may have potential as a biomarker for risk of development of metastatic disease.
