Generation of tumors in transgenic mice expressing the SV40 T antigen under the control of ovarian-specific promoter 1.
OBJECTIVE
The ovarian-specific promoter, OSP-1, which was cloned from the transcript of a rat retrovirus-like element specifically expressed in ovarian tissue, was tested for its ability to drive ovary-specific transcription in transgenic mice.


METHODS
Transgenic mice were generated with the lacZ reporter gene (OSP-lacZ) or the early region of SV40 virus (OSP-TAg) placed under the control of the OSP-1 promoter. OSP-lacZ and OSP-TAg transgenic animals were examined, respectively, for the expression of lacZ (OSP-lacZ) or the development of tumors (OSP-TAg).


RESULTS
The expression of lacZ in the resulting OSP-lacZ mice was restricted to the ovary as determined by X-gal staining of multiple organs. Immunohistochemical detection of beta-galactosidase showed lacZ expression mainly in the granulosa cells and ovarian surface epithelial cells. OSP-TAg mice developed tumors in a variety of tissues, including unilateral granulosa cell tumors in two of three female founder mice. In the contralateral ovary of one mouse with a granulosa cell tumor, there were alterations in the ovarian surface epithelial cells suggestive of preneoplasia.


CONCLUSIONS
Although the OSP-1 promoter was able to restrict reporter gene expression to the ovary in transgenic mice, the expression of TAg in the OSP-TAg mice resulted in ovarian tumors as well as tumors in numerous other organs. This indicated that although transcription from the OSP-1 promoter occurs predominantly in the ovary, this promoter is sufficiently leaky in cells in other tissues to permit their tumorigenic conversion by SV40 TAg.
Garson
Kenneth
K
Department of Cellular and Molecular Medicine, University of Ottawa and Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada.
Macdonald
Elizabeth
E
Dubé
Manon
M
Bao
Rudi
R
Hamilton
Thomas C
TC
Vanderhyden
Barbara C
BC
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D007763:Lac Operon / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009693:Nucleic Acid Hybridization; D010051:Ovarian Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D013539:Simian virus 40 / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
D000957:Antigens, Viral, Tumor; D012333:RNA, Messenger