Reference SummaryNakagawa H, Oncogene 1997 Mar 13;14(10):1185-90

Title

 The targeting of the cyclin D1 oncogene by an Epstein-Barr virus promoter in transgenic mice causes dysplasia in the tongue, esophagus and forestomach.

Authors

 Nakagawa H; Wang TC; Zukerberg L; Odze R; Togawa K; May GH; Wilson J; Rustgi AK

Journal

 Oncogene

Volume

 14

Issue

 10

Year

 1997

Pages

 1185-90

Abstract

 Cyclin D1 in cooperation with its major catalytic partners, cyclin-dependent kinases cdk4 and cdk6, facilitates progression through the G1 phase of the eukaryotic cell cycle, in part through phosphorylation of the retinoblastoma protein. Cyclin D1's oncogenic properties have been suggested by its cooperation with ras or adenovirus E1a to transform cultured cells, as well its overexpression in transgenic mice that leads to breast cancer. Activated by a number of different mechanisms in human cancers, the cyclin D1 gene is frequently amplified in squamous epithelial cancers derived from the head/neck and esophageal regions. In order to study the functional consequences of cyclin D1 overexpression in these squamous epithelial specific sites, we have linked the Epstein-Barr virus ED-L2 promoter to the human cyclin D1 cDNA and utilized this transgene to generate founder lines. This transgene is transcribed specifically in the tongue, esophagus and forestomach, all sharing a stratified squamous epithelium. The transgene protein product localizes to the basal and suprabasal compartments of these squamous epithelial tissues, and mice from different lines develop dysplasia, a prominent precursor to carcinoma, by 16 months of age in contrast to age-matched wild-type mice. This transgenic model is useful in demonstrating cyclin D1 may be a tumor initiating event in aero-upper digestive squamous epithelial tissues.

Links

 J:48597 – MGI References
9121767 – National Library of Medicine/PubMed

Strain Notes

Strain Note
FVB/N-Tg(L2hD)#Aru Expression of the "L2hD" transgene was reported to not be detected brain, heart, lungs, liver, pancreas, glandular stomach, large intestine, small intestine, kidney, spleen, ovaries, and testis of these mice.
The "L2hD" transgene was reported to be expressed in the esophagus, tongue, forestomach, and skin of these mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N-Tg(L2hD)#Aru Esophagus carcinoma Esophagus

0
FVB/N-Tg(L2hD)#Aru Esophagus dysplasia Esophagus

100
FVB/N Esophagus dysplasia Esophagus

0
FVB/N-Tg(L2hD)#Aru Forestomach carcinoma Forestomach

0
FVB/N-Tg(L2hD)#Aru Forestomach dysplasia Forestomach

100
FVB/N Forestomach dysplasia Forestomach

0
FVB/N-Tg(L2hD)#Aru Tongue carcinoma Tongue

0
FVB/N-Tg(L2hD)#Aru Tongue dysplasia Tongue

100
FVB/N Tongue dysplasia Tongue

0