Reference SummaryMueller A, Cancer Res 1997 Dec 15;57(24):5542-9

Title

A transgenic mouse model with cyclin D1 overexpression results in cell cycle, epidermal growth factor receptor, and p53 abnormalities.

Authors

Mueller A; Odze R; Jenkins TD; Shahsesfaei A; Nakagawa H; Inomoto T; Rustgi AK

Journal

Cancer Res

Volume

57

Issue

24

Year

1997

Pages

5542-9

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.

Links

J:45230 – MGI References
9407965 – National Library of Medicine/PubMed

Strain Notes

Strain Note
FVB/N Expression of the wild type allele of the Trp53 gene was reported to not be detected in the esophagus and tongue of these mice.
The wild type alleles of the Ccnd1, Cdk4, Egfr, and Pcna genes was reported to be expressed n the esophagus and tongue of these mice.
FVB/N-Tg(L2hD)#Aru Expression of the wildtype allele of the Trp53 gene was reported to not be detected in the esophagus and tongue of these mice.
The "L2hD" transgene and the wild type alleles of the Ccnd1, Cdk4, Egfr, and Pcna genes were reported to be expressed in the esophagus and tongue of these mice.
The "L2hD" transgene was reported to be expressed in the forestomach of these mice.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N Esophagus dysplasia Esophagus

0

FVB/N-Tg(L2hD)#Aru Esophagus dysplasia Esophagus

100

FVB/N Tongue dysplasia Tongue

0

FVB/N-Tg(L2hD)#Aru Tongue dysplasia Tongue

100