Md. Lairmore et al., Squamous epithelial proliferation induced by walleye dermal sarcoma retrovirus cyclin in transgenic mice, P NAS US, 97(11), 2000, pp. 6114-6119
Citations number
46
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Walleye dermal sarcoma (WDS) is a common disease of walleye fish in the Uni
ted States and Canada, These proliferative lesions are present autumn throu
gh winter and regress in the spring. Walleye dermal sarcoma virus (WDSV), a
retrovirus distantly related to other members of the family Retroviridae,
has been etiologically linked to the development of WDS. We have reported t
hat the D-cyclin homologue [retroviral (rv) cyclin] encoded by WDSV rescues
yeast conditionally deficient for cyclin synthesis from growth arrest and
that WDSV-cyclin mRNA is present in developing tumors. These data strongly
suggest that the rv-cyclin plays a central role in the development of WDS,
To test the ability of the WDSV rv-cyclin to induce cell proliferation, we
have generated transgenic mice expressing the rv-cyclin in squamous epithel
ia from the bovine keratin-5 promoter. The transgenic animals were smaller
than littermates, had reduced numbers of hair follicles, and transgenic fem
ales did not lactate properly, Following injury the transgenic animals deve
loped severe squamous epithelial hyperplasia and dysplasia with ultrastruct
ural characteristics of neoplastic squamous epithelium. Immunocytochemistry
studies demonstrated that the hyperplastic epithelium stained positive for
cytokeratin and were abnormally differentiated. Furthermore, the rv-cyclin
protein was detected in the thickened basal cell layers of the proliferati
ng lesions, These data are the first to indicate that the highly divergent
WDSV rv-cyclin is a very potent stimulator of eukaryotic cell proliferation
and to demonstrate the potential of a cyclin homologue encoded by a retrov
irus to induce hyperplastic skin lesions.