Faculty Collaboration Database

Cyclin D1 overexpression combined with N-nitrosomethylbenzylamine increases dysplasia and cellular proliferation in murine esophageal squamous epithelium. Oncogene 1999 Jan 07;18(1):59-66

Date

02/02/1999

Pubmed ID

9926920

DOI

10.1038/sj.onc.1202296

Scopus ID

2-s2.0-0033531242 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

We previously described the oral-esophageal tissue-specific expression of cyclin D1 with the Epstein-Barr virus ED-L2 promoter in transgenic mice, and resulting dysplasia. Given the evidence for an interplay between environmental and genetic factors in esophageal squamous carcinogenesis, the aim of this study was to determine the potential cooperation of the nitrosamine compound N-nitrosomethylbenzylamine (NMBA), an esophageal specific carcinogen, in the cyclin D1 transgenic mice. NMBA was first demonstrated to induce dysplasia in two strains of inbred mice, C57BL/6 and FVB/N. Subcutaneous NMBA was then administrated to wild type and transgenic mice beginning at 4 weeks of age. Mice were monitored for the duration of the study for general appearance, activity and weight, and were euthanized at 12 and 15 months. Histopathologic analysis revealed increased severity of dysplasia in cyclin D1 mice treated with NMBA compared with treated age-matched wild-type mice and untreated mice. There was also increased proliferating cell nuclear antigen (PCNA) expression in the esophagi of NMBA treated cyclin D1 mice. Taken together, these findings suggest that a genetic alteration, specifically cyclin D1 overexpression and a chemical carinogen, NMBA, may cooperate to increase the severity of esophageal squamous dysplasia, a prominent precursor to carcinoma.

Author List

Jenkins TD, Mueller A, Odze R, Shahsafaei A, Zukerberg LR, Kent R, Stoner GD, Rustgi AK

MESH terms used to index this publication - Major topics in bold

Animals
Carcinogens
Cell Division
Cyclin D1
Dimethylnitrosamine
Epithelium
Esophageal Neoplasms
Gene Expression
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasms, Squamous Cell