科學(xué)家分析了與乳腺癌有關(guān)聯(lián)的基因的統(tǒng)計數(shù)據(jù)，結(jié)果發(fā)現(xiàn)了一個特效的分子靶標——這是已知的第二個分子靶標。它有可能對藥物治療做出響應(yīng),。出現(xiàn)乳腺癌是因為多種突變或基因表達水平的變化,。某些腫瘤過度表達ERBB2受體,；醫(yī)生已經(jīng)成功使用了一種稱為曲妥珠單抗的單克隆抗體阻止了這種受體在乳腺癌患者體內(nèi)的活動,。
Arul Chinnaiyan及其同事進行了一場元研究，從而分析了乳腺癌的基因過度表達,，結(jié)果發(fā)現(xiàn),，除了ERBB2，AGTR1受體在一些腫瘤中也有類似的過度表達,。這組作者使用了此前開發(fā)的一種方法發(fā)現(xiàn)了其他研究獲得的31個乳腺癌譜數(shù)據(jù)中的過度表達的基因,。ERBB2 在這項元研究中的得分最高；與癌癥有關(guān)的AGTR1是得分第二高的基因,。這組作者還進行了細胞和動物移植研究,，從而檢查了AGTR1過度表達的效應(yīng)，結(jié)果證明了這種受體看上去并不影響腫瘤增殖,，而是增加癌細胞的入侵行為。一種常用藥氯沙坦已知可以抑制AGTR1,。(生物谷Bioon.com)
生物谷推薦原始出處：
PNAS June 1, 2009, doi: 10.1073/pnas.0900351106
AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist
Daniel R. Rhodesa,b,1, Bushra Ateeqa,b,1, Qi Caoa,b,1, Scott A. Tomlinsa,b,1, Rohit Mehraa,b, Bharathi Laxmana,b, Shanker Kalyana-Sundarama,b, Robert J. Lonigroa,c, Beth E. Helgesona,b, Mahaveer S. Bhojanic,d, Alnawaz Rehemtullac,d, Celina G. Kleerb,c, Daniel F. Hayesc,e, Peter C. Lucasb,c, Sooryanarayana Varamballya,b,c and Arul M. Chinnaiyana,b,c,f,g,2
Breast cancer patients have benefited from the use of targeted therapies directed at specific molecular alterations. To identify additional opportunities for targeted therapy, we searched for genes with marked overexpression in subsets of tumors across a panel of breast cancer profiling studies comprising 3,200 microarray experiments. In addition to prioritizing ERBB2, we found AGTR1, the angiotensin II receptor type I, to be markedly overexpressed in 10–20% of breast cancer cases across multiple independent patient cohorts. Validation experiments confirmed that AGTR1 is highly overexpressed, in several cases more than 100-fold. AGTR1 overexpression was restricted to estrogen receptor-positive tumors and was mutually exclusive with ERBB2 overexpression across all samples. Ectopic overexpression of AGTR1 in primary mammary epithelial cells, combined with angiotensin II stimulation, led to a highly invasive phenotype that was attenuated by the AGTR1 antagonist losartan. Similarly, losartan reduced tumor growth by 30% in AGTR1-positive breast cancer xenografts. Taken together, these observations indicate that marked AGTR1 overexpression defines a subpopulation of ER-positive, ERBB2-negative breast cancer that may benefit from targeted therapy with AGTR1 antagonists, such as losartan.
