Research article summary (published 30 Aug 2009):

Cyclin D1 overexpression increases susceptibility to 4-nitroquinoline-1-oxide-induced dysplasia and neoplasia in murine squamous oral epithelium.

Full Abstract

The cyclin D1 oncogene is frequently amplified/overexpressed in oral squamous cell carcinomas. Mice with overexpression of cyclin D1 targeted to the stratified squamous epithelia of the tongue, esophagus, and forestomach develop a phenotype of epithelial dysplasia at these sites. In this study, we examined the effect of cyclin D1 overexpression on susceptibility of mice to carcinogen-induced tumorigenesis, using 4-nitroquinoline-1-oxide (4NQO), an established potent oral carcinogen in mice. Cyclin D1 overexpressing mice and nontransgenic littermates were administered 4NQO (20 or 50 parts per million (ppm) in the drinking water) for 8 wk and monitored for an additional 16 wk. Histopathological analyses of the tongue revealed significantly higher severity of dysplasia in the cyclin D1 overexpression mice, compared with nontransgenic controls and with untreated controls. Moreover, only the cyclin D1 overexpression mice developed neoplastic lesions in the oro-esophageal epithelia. Examination of the dysplastic and neoplastic lesions revealed abnormal proliferation. Our findings suggest that cyclin D1 overexpression enhances susceptibility to carcinogen-induced oral tumorigenesis. These results underscore the importance of cyclin D1 in the process of oral neoplastic development. Further, they emphasize the value of this transgenic model to study the pathogenesis of oral precancer and cancer and establish it as a model system to test candidate agents for chemoprevention of upper aero-digestive cancer.

Author information

Author/s: Wilkey, Jonathan F (JF); Buchberger, Glenn (G); Saucier, Kirsten (K); Patel, Salony M (SM); Eisenberg, Ellen (E); Nakagawa, Hiroshi (H); Michaylira, Carmen Z (CZ); Rustgi, Anil K (AK); Mallya, Sanjay M (SM);

Affiliation: Section of Oral & Maxillofacial Radiology, University of Connecticut School of Dental Medicine, Farmington, Connecticut 06030, USA.

Grants: DE0014773 (Agency:NIDCR NIH HHS) ; F32-DK07523 (Agency:NIDDK NIH HHS) ; P01-CA098101 (Agency:NCI NIH HHS) ; R01-DK077005 (Agency:NIDDK NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Molecular carcinogenesis (Mol Carcinog), published in United States. (Language: eng)

Reference: 2009-Sep; vol 48 (issue 9) : pp 853-61

Dates: Created 2009/09/01; Completed 2009/09/16;

PMID: 19263437, status: MEDLINE (last retrieved date: 9/16/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

4-Nitroquinoline-1-oxide - toxicity Animals Blotting, Northern Carcinogens - toxicity Cell Differentiation - drug effects Cell Proliferation - drug effects Cyclin D1 - genetics; metabolism Cyclin-Dependent Kinase Inhibitor p16 - metabolism Disease Models, Animal Epithelium - drug effects; metabolism; pathology Female Gene Expression

Gene Expression Genetic Predisposition to Disease Immunohistochemistry Keratin-5 - metabolism Ki-67 Antigen - metabolism Male Mice Mice, Transgenic Mouth Mucosa - drug effects; metabolism; pathology Mouth Neoplasms - chemically induced; genetics; metabolism Precancerous Conditions - chemically induced; genetics; metabolism Transgenes - genetics

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Carcinogens (0) ; Cyclin-Dependent Kinase Inhibitor p16 (0) ; Keratin-5 (0) ; Ki-67 Antigen (0) ; Cyclin D1 (136601-57-5) ; 4-Nitroquinoline-1-oxide (56-57-5)

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