Induction of ovarian cancer by defined multiple genetic changes in a mouse model system Journal Article
| Authors: | Orsulic, S.; Li, Y.; Soslow, R. A.; Vitale-Cross, L. A.; Gutkind, J. S.; Varmus, H. E. |
| Article Title: | Induction of ovarian cancer by defined multiple genetic changes in a mouse model system |
| Abstract: | We have developed a mouse model for ovarian carcinoma by using an avian retroviral gene delivery technique for the introduction of multiple genes into somatic ovarian cells of adult mice. Ovarian cells from transgenic mice engineered to express the gene encoding the avian receptor TVA were efficiently infected in vitro with multiple vectors carrying coding sequences for oncogenes and marker genes. When target cells were derived from TVA transgenic mice deficient for p53, the addition of any two of the oncogenes c-myc, K-ras, and Akt were sufficient to induce ovarian tumor formation when infected cells were injected at subcutaneous, intraperitoneal, or ovarian sites. We demonstrated that the ovarian surface epithelium is the precursor tissue for these ovarian carcinomas, and that introduction of oncogenes causes phenotypic changes in the ovarian surface epithelial cells. The induced ovarian tumors in mice resembled human ovarian carcinomas in their rapid progression and intraperitoneal metastatic spread. Copyright © 2002 Cell Press. |
| Keywords: | protein kinase b; controlled study; oncoprotein; gene sequence; genetics; proto-oncogene proteins; cancer growth; nonhuman; ovarian neoplasms; mouse; phenotype; animal; metabolism; mouse mutant; animals; mice; mice, knockout; actin; animal tissue; cell division; metastasis; ovary cancer; gene expression; animal experiment; animal model; pathology; protein serine threonine kinase; protein p53; physiology; virus receptor; carcinogenesis; gene transfer; transgenic mouse; viral gene delivery system; gene vector; mus musculus; genetic vectors; mice, transgenic; receptors, virus; cell transformation, neoplastic; disease model; enzyme immunoassay; immunoenzyme techniques; aves; cancer genetics; oncogene; alkaline phosphatase; blotting, western; genetic engineering; cell transformation; protein-serine-threonine kinases; ovary tumor; genes, myc; western blotting; proto-oncogene proteins c-akt; carcinoma; ovary carcinoma; retrovirus vector; epithelium cell; tumor suppressor protein p53; calcium binding protein; calcium-binding proteins; epithelium; oncogene k ras; genes, ras; disease models, animal; actins; oncogene c myc; genetic code; oncogene ras; oncogene myc; gene transfer techniques; avian protein; avian proteins; akt1 protein, human; humans; human; female; priority journal; article; tva receptor |
| Journal Title: | Cancer Cell |
| Volume: | 1 |
| Issue: | 1 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2002-02-01 |
| Start Page: | 53 |
| End Page: | 62 |
| Language: | English |
| DOI: | 10.1016/s1535-6108(01)00002-2 |
| PUBMED: | 12086888 |
| PROVIDER: | scopus |
| PMCID: | PMC2267863 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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