首席科学家Nature后又发癌症靶位文章

　　

生物通报道，密歇根大学转化病理学中心，癌症综合研究所等处的科研人员在PNAS发表文章AGTR1 over-expression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist，找到一个新的乳腺癌治疗靶位。

 

文章通讯作者是来自密歇根大学的Arul M Chinnaiyan，目前担任病病理系教授，病理信息研究中心主任，癌症生物信息研究中心主任。Arul M Chinnaiyan是位高产的科学家，仅2009年，到目前为止就已经发表了17篇文章，其中第一篇发表在Nature上，Transcriptome sequencing to detect gene fusions in cancer. Nature. 2009 Jan 11。（Arul M Chinnaiyan主页：http://www.pathology.med.umich.edu/dynamo/chinnaiyan/index.jsp）

 

Arul M Chinnaiyan等人分析了与乳腺癌有关联的基因的统计数据，结果发现了一个新的靶位——这是已知的乳腺癌的第二个分子靶位。这一靶位可能指导最新的药物设计。

 

Arul Chinnaiyan及其同事分析了乳腺癌的基因过度表达情况，结果发现，AGTR1受体一些乳腺癌患者细胞中过度表达。研究人员还检测了了AGTR1过度表达的效应，结果证明了这AGTR1受体看上去并不影响肿瘤增殖，而是增加癌细胞的入侵行为。一种常用药氯沙坦已知可以抑制AGTR1。

 

生物通推荐原文检索：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

【Abstract】

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.