title: A transgenic mouse model with cyclin D1 overexpression results in cell cycle, epidermal growth factor receptor, and p53 abnormalities.
abstract: The cyclin D1 oncogene is critical in the progression of the cell cycle through the G1 phase. It is frequently overexpressed in squamous cell carcinomas originating from the head/neck and esophagus. Yet, the functional consequences of aberrant cyclin D1 overexpression are not entirely understood apart from increased cell proliferation. To address this question, we have developed a transgenic mouse model in which the EBV ED-L2 promoter targets cyclin D1 to the stratified squamous epithelium in a tissue-specific fashion to the tongue and esophagus, thereby resulting in a dysplastic phenotype. We now demonstrate that the dysplastic phenotype is associated with increased cell proliferation based on proliferating cell nuclear antigen overexpression and abnormalities in cyclin-dependent kinase 4, epidermal growth factor receptor, and p53. In aggregate, these studies suggest that alterations in certain oncogenes and tumor suppressor genes occur early during head/neck and esophageal carcinogenesis.
authors.affiliation: Massachusetts General Hospital, and Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston 02114, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mueller
authors.forename: R
authors.initials: R
authors.lastname: Odze
authors.forename: T D
authors.initials: TD
authors.lastname: Jenkins
authors.forename: A
authors.initials: A
authors.lastname: Shahsesfaei
authors.forename: H
authors.initials: H
authors.lastname: Nakagawa
authors.forename: T
authors.initials: T
authors.lastname: Inomoto
authors.forename: A K
authors.initials: AK
authors.lastname: Rustgi
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D004848:Epithelium / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins; D014059:Tongue / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D066246:ErbB Receptors; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases