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AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist
Proceedings of the National Academy of Sciences of the United States of America, 06/26/09

Rhodes DR et al. - In a study to identify additional opportunities for targeted therapy, it was concluded 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.

• To identify additional opportunities for targeted therapy, genes were sought with marked overexpression in subsets of tumors across a panel of breast cancer profiling studies comprising 3200 microarray experiments.

• In addition to prioritizing ERBB2, AGTR1 was found to be markedly overexpressed in 10–20% of breast cancer cases across multiple independent pt 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.
• Losartan reduced tumor growth by 30% in AGTR1-positive breast cancer xenografts.

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