Int J Biol Sci 2016; 12(4):381-388. doi:10.7150/ijbs.12947
Targeting Oncogenes into a Defined Subset of Mammary Cells Demonstrates That the Initiating Oncogenic Mutation Defines the Resulting Tumor Phenotype
1. Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA;
Breast cancers exhibit high intertumoral heterogeneity in genetic alterations as well as histopathological and other phenotypic characteristics. The contribution of the initiating oncogenic mutation to tumor phenotype remains controversial, largely due to the technical difficulties in delivering genetic alterations into well-defined subsets of mammary epithelial cells. To examine how different initiating oncogenes drive tumor phenotype, we somatically delivered two oncogenes (ErbB2, PyMT) into a narrow and distinct subset of the mouse mammary epithelium defined by the expression of the progenitor marker keratin 6a (Krt6a), and compared the phenotypes of the resulting mammary tumors. While PyMT-induced tumors were well-differentiated and displayed glandular and papillary features, ErbB2-induced tumors were poorly differentiated and exhibited epithelial-to-mesenchymal transition as well as β-catenin activation. These in vivo data demonstrate that the initiating oncogene plays a key role in driving mammary tumor phenotype.
Keywords: Keratin 6a, PyMT, ErbB2, Breast Cancer, RCAS, tva
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How to cite this article:
Holloway KR, Sinha VC, Bu W, Toneff M, Dong J, Peng Y, Li Y. Targeting Oncogenes into a Defined Subset of Mammary Cells Demonstrates That the Initiating Oncogenic Mutation Defines the Resulting Tumor Phenotype. Int J Biol Sci 2016; 12(4):381-388. doi:10.7150/ijbs.12947. Available from http://www.ijbs.com/v12p0381.htm