美國研究人員稱,，他們發(fā)現(xiàn)名為MTDH的基因在乳腺癌患者體內(nèi)起關(guān)鍵作用，其增加了癌細(xì)胞擴(kuò)散的幾率并且能夠抵抗化療,。有關(guān)專家指出，針對(duì)該基因研發(fā)新藥物將具有廣闊前景。相關(guān)研究成果發(fā)表在1月5日出版的《癌細(xì)胞》雜志上,。
阻止癌細(xì)胞擴(kuò)散相當(dāng)重要。研究顯示,，在癌細(xì)胞沒有擴(kuò)散的病人中,，超過98%的病人能存活5年以上，而在癌細(xì)胞已經(jīng)擴(kuò)散的病人中,，只有27%的人能夠存活,。
美國新澤西癌癥研究院的米歇爾·雷斯和普林斯頓大學(xué)的康一斌(音)采用了幾種方法來尋找使腫瘤擴(kuò)散的基因，他們調(diào)用了龐大的腫瘤細(xì)胞數(shù)據(jù)庫,，發(fā)現(xiàn)身患嚴(yán)重乳腺癌的病人體內(nèi),，其8號(hào)人類染色體的一小部分被重復(fù)了多次。一般來說,，大多數(shù)正常DNA序列的一個(gè)基因僅僅有2個(gè)副本,，但這部分基因的副本多達(dá)8個(gè)。
接著,，研究人員分析了采自于250個(gè)病人的乳腺癌基因樣本,，以尋找其中的遺傳變異。研究發(fā)現(xiàn),，在富有攻擊力的腫瘤中,，其MTDH基因過度活躍或被過度表達(dá),。該基因不僅能使腫瘤細(xì)胞緊緊地附著在發(fā)病區(qū)域附近器官的血管上，還能大大減弱抗癌藥物的作用使腫瘤細(xì)胞產(chǎn)生耐藥性,。
研究人員接著在實(shí)驗(yàn)鼠身上注射了采自于具有該基因變異病人的腫瘤細(xì)胞,，發(fā)現(xiàn)老鼠體內(nèi)出現(xiàn)了會(huì)擴(kuò)散的腫瘤，這些腫瘤也抑制了傳統(tǒng)的化療藥物如紫杉醇的治療效果,。
但當(dāng)研究人員對(duì)這些腫瘤進(jìn)行遺傳修改,，抑制了MTDH基因后，腫瘤細(xì)胞不再擴(kuò)散并且對(duì)化學(xué)療法不再有抵抗力,。研究人員說,，MTDH可能在包括前列腺癌在內(nèi)的許多其他類癌癥中也起主要作用。
研究人員希望,，他們的發(fā)現(xiàn)將有助于開發(fā)出不僅能阻止腫瘤細(xì)胞擴(kuò)散而且對(duì)治療反應(yīng)更好的藥物,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer Cell，Volume 15, Issue 1, 9-20,，Michael Reiss,，Yibin Kang
MTDH Activation by 8q22 Genomic Gain Promotes Chemoresistance and Metastasis of Poor-Prognosis Breast Cancer
Guohong Hu1,Robert A. Chong1,6,Qifeng Yang2,6,7,Yong Wei1,Mario A. Blanco1,Feng Li1,Michael Reiss3,4,Jessie L.-S. Au5,Bruce G. Haffty2andYibin Kang1,4,,
1 Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
2 Department of Radiation Oncology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA
3 Department of Internal Medicine, The Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
4 Breast Cancer Program, The Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
5 College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
6 These authors contributed equally to this work
7 Present address: Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012, China
Summary
Targeted therapy for metastatic diseases relies on the identification of functionally important metastasis genes from a large number of random genetic alterations. Here we use a computational algorithm to map minimal recurrent genomic alterations associated with poor-prognosis breast cancer. 8q22 genomic gain was identified by this approach and validated in an extensive collection of breast tumor samples. Regional gain of 8q22 elevates expression of the metastasis gene metadherin (MTDH), which is overexpressed in more than 40% of breast cancers and is associated with poor clinical outcomes. Functional characterization of MTDH revealed its dual role in promoting metastatic seeding and enhancing chemoresistance. These findings establish MTDH as an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk.
