title: Targeting Oncogenes into a Defined Subset of Mammary Cells Demonstrates That the Initiating Oncogenic Mutation Defines the Resulting Tumor Phenotype.
abstract: 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.
authors.affiliation: 1. Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA;
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Holloway
authors.affiliation: 1. Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA;; 2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Vidya C
authors.initials: VC
authors.lastname: Sinha
authors.affiliation: 1. Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA;; 2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Bu
authors.affiliation: 2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Toneff
authors.affiliation: 2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.affiliation: 3. National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China;; 4. Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Peng
authors.affiliation: 1. Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA;; 2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D005260:Female; D053553:Keratin-6 / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D053553:Keratin-6; D018719:Erb-b2 Receptor Tyrosine Kinases; D051176:beta Catenin
keywords: Breast Cancer; ErbB2; Keratin 6a; PyMT; RCAS; tva