Transcriptomic analysis of mammary tumors from MMTV-ErbB2 transgenic mice

The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.

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Castellanos-Martín A, Castillo-Lluva S, Sáez-Freire Mdel M, Blanco-Gómez A, Hontecillas-Prieto L, Patino-Alonso C, Galindo-Villardon P, Pérez Del Villar L, Martín-Seisdedos C, Isidoro-Garcia M, Abad-Hernández MM, Cruz-Hernández JJ, Rodríguez-Sánchez CA, González-Sarmiento R, Alonso-López D, De Las Rivas J, García-Cenador B, García-Criado J, Lee DY, Bowen B, Reindl W, Northen T, Mao JH, Pérez-Losada J