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Generation of Tumors in Transgenic Mice Expressing the SV40 T Antigen Under the Control of Ovarian-Specific Promoter 1

Elizabeth Macdonald, MSc

Manon Dubé, MSc

Rudi Bao, MD

Thomas C. Hamilton, PhD

Department of Cellular and Molecular Medicine, University of Ottawa and Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada; and Ovarian Cancer Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania

Barbara C. Vanderhyden, PhD

Centre for Cancer Therapeutics, Ottawa Regional Cancer Centre, 3rd Floor, 503 Smyth Road, Ottawa, ON, Canada, K1H 1C4

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 ß-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 wee 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.

Key Words: Ovarian cancer • ovary • OSP-1 promoter • granulosa tumor • transgenic

Journal of the Society for Gynecologic Investigation, Vol. 10, No. 4, 244-250 (2003)
DOI: 10.1016/S1071-55760300073-X


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