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Shahenda M El-Naggar Department of Biochemistry and Molecular Biology,
Department of Pathology and
Department of Medicine,
Research Resource Center, University of Louisville, Louisville, Kentucky 40202, USA,
James Graham Cancer Center, University of Louisville, 580 South Preston St Baxter II, 324, Louisville, Kentucky 40202, USA

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Mohammad T Malik Department of Biochemistry and Molecular Biology,
Department of Pathology and
Department of Medicine,
Research Resource Center, University of Louisville, Louisville, Kentucky 40202, USA,
James Graham Cancer Center, University of Louisville, 580 South Preston St Baxter II, 324, Louisville, Kentucky 40202, USA

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Alvin Martin Department of Biochemistry and Molecular Biology,
Department of Pathology and
Department of Medicine,
Research Resource Center, University of Louisville, Louisville, Kentucky 40202, USA,
James Graham Cancer Center, University of Louisville, 580 South Preston St Baxter II, 324, Louisville, Kentucky 40202, USA

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Joseph P Moore Department of Biochemistry and Molecular Biology,
Department of Pathology and
Department of Medicine,
Research Resource Center, University of Louisville, Louisville, Kentucky 40202, USA,
James Graham Cancer Center, University of Louisville, 580 South Preston St Baxter II, 324, Louisville, Kentucky 40202, USA

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Mary Proctor Department of Biochemistry and Molecular Biology,
Department of Pathology and
Department of Medicine,
Research Resource Center, University of Louisville, Louisville, Kentucky 40202, USA,
James Graham Cancer Center, University of Louisville, 580 South Preston St Baxter II, 324, Louisville, Kentucky 40202, USA

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Tariq Hamid Department of Biochemistry and Molecular Biology,
Department of Pathology and
Department of Medicine,
Research Resource Center, University of Louisville, Louisville, Kentucky 40202, USA,
James Graham Cancer Center, University of Louisville, 580 South Preston St Baxter II, 324, Louisville, Kentucky 40202, USA

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Sham S Kakar Department of Biochemistry and Molecular Biology,
Department of Pathology and
Department of Medicine,
Research Resource Center, University of Louisville, Louisville, Kentucky 40202, USA,
James Graham Cancer Center, University of Louisville, 580 South Preston St Baxter II, 324, Louisville, Kentucky 40202, USA

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The pituitary tumor transforming gene (PTTG)/securin is an oncogene that is involved in cell cycle regulation and sister chromatid separation. PTTG is highly expressed in various tumors including ovarian tumors, suggesting that PTTG may play a role in ovarian tumorigenesis. Overexpression of PTTG resulted in induction of cellular transformation in vitro and tumor formation in nude mice. To ascertain PTTG function in ovarian tumorigenesis, we generated a transgenic mouse model of PTTG by cloning PTTG cDNA downstream of Mullerian inhibitory substance type II receptor gene promoter (MISIIR) in order to target the ovarian surface epithelium. By screening of transgenic animals, we identified five founders (four males and one female). Using the four male founders, we developed four transgenic lines. PTTG expression was increased in ovarian surface epithelium, ovarian granulosa cells, as well as in the pituitary gland. Transgenic females did not develop any visible ovarian tumors at 8–10 months of age; however, there was an overall increase in the corpus luteum mass in transgenic ovary, suggesting increased luteinization. These changes were associated with an increase in serum LH and testosterone levels. In addition, there was a generalized hypertrophy of the myometrium of MISIIR–PTTG transgenic uteri with cystic glandular and hyperplasia of the endometrium. Based on these results, we conclude that the overexpression of PTTG may be required to initiate precancerous conditions but is not sufficient to induce ovarian tumorigenesis and may require another partner to initiate cellular transformation.

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