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Female mice chimeric for expression of the simian virus 40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer.
- Source :
-
Cancer research [Cancer Res] 2003 Mar 15; Vol. 63 (6), pp. 1389-97. - Publication Year :
- 2003
-
Abstract
- In women, >80% of malignant ovarian tumors are of epithelial origin. Early detection of these tumors is very challenging,and extensive i.p. dissemination is common by the time of diagnosis. The lack of adequate geneticmouse models of ovarian carcinomas significantly delays advances in early detection and treatment. We report that female transgenic mice expressing the transforming region of SV40 under control of the Mullerian inhibitory substance type II receptor gene promoter develop bilateral ovarian tumors in approximately 50% of cases. Histologically, these tumors are poorly differentiated carcinomas with occasional cysts and papillary structures present at the surface of the ovary. These tumors disseminate i.p., invade omentum, and form ascites as do human ovarian carcinomas. The epithelial origin of these tumors is supported by detection of cytokeratins 8 and 19, and the absence of alpha-inhibin, a protein characteristically expressed in normal granulosa cells and most granulosa cell tumors. Cell lines derived from the ascites exhibit the properties of epithelial ovarian cancer, such as anchorage-independent growth, tumorigenicity in immunocompromised mice, expression of epithelial cell markers, and organotropic implantation. The availability of a transgenic mouse model of disseminated ovarian carcinoma and respective cell lines should advance our understanding of this neoplasm, and serve as a useful tool for the evaluation of emerging detection and treatment strategies.
- Subjects :
- Animals
Antigens, Polyomavirus Transforming biosynthesis
Chimera genetics
Disease Models, Animal
Epithelium metabolism
Epithelium pathology
Epithelium physiology
Female
Humans
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Transgenic
Ovarian Neoplasms metabolism
Ovarian Neoplasms pathology
Pregnancy
Promoter Regions, Genetic
Receptors, Peptide biosynthesis
Receptors, Transforming Growth Factor beta
Regulatory Sequences, Nucleic Acid
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Tumor Cells, Cultured
Antigens, Polyomavirus Transforming genetics
Ovarian Neoplasms genetics
Receptors, Peptide genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 63
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 12649204