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

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Abstract

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 β-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.

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Authors and Affiliations

  1. Centre for Cancer Therapeutics, Department of Cellular and Molecular Medicine, University of Ottawa and Ottawa Regional Cancer Centre, 3rd Floor, 503 Smyth Road, Ottawa, Ontario, Canada, K1H 1C4

    Kenneth Garson PhD, Elizabeth Macdonald MSc, Manon Dubé MSc, Rudi Bao MD, Thomas C. Hamilton PhD & Barbara C. Vanderhyden PhD

  2. Ovarian Cancer Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Kenneth Garson PhD, Elizabeth Macdonald MSc, Manon Dubé MSc, Rudi Bao MD, Thomas C. Hamilton PhD & Barbara C. Vanderhyden PhD

Authors
  1. Kenneth Garson PhD
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  2. Elizabeth Macdonald MSc
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  3. Manon Dubé MSc
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  4. Rudi Bao MD
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  5. Thomas C. Hamilton PhD
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  6. Barbara C. Vanderhyden PhD
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Additional information

This work was supported by a grant from the National Institutes of Health (CA 84242) to TCH and BCV.

The authors would like to thank Audri Brewster for technical assistance and to acknowledge Dr. Robert D. Cardiff for analyzing and providing pathology reports on tumors arising in the OSP-TAg mice.

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Garson, K., Macdonald, E., Dubé, M. et al. Generation of Tumors in Transgenic Mice Expressing the SV40 T Antigen Under the Control of Ovarian-Specific Promoter 1. Reprod. Sci. 10, 244–250 (2003). https://doi.org/10.1016/S1071-5576(03)00073-X

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  • DOI: https://doi.org/10.1016/S1071-5576(03)00073-X

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