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- Title
Transient depletion of p53 followed by transduction of c-Myc and K-Ras converts ovarian stem-like cells into tumor-initiating cells.
- Authors
Motohara, Takeshi; Masuko, Sachiko; Ishimoto, Takatsugu; Yae, Toshifumi; Onishi, Nobuyuki; Muraguchi, Teruyuki; Hirao, Atsushi; Matsuzaki, Yumi; Tashiro, Hironori; Katabuchi, Hidetaka; Saya, Hideyuki; Nagano, Osamu
- Abstract
Although the existence of tumor-initiating cells (T-ICs) in several types of human cancer has been documented, the contribution of somatic stem cells to the development of T-ICs has remained unclear. Here, we show that normal mouse ovary contains epithelial cell adhesion molecule (EpCAM)-expressing stem-like cells that possess the ability to differentiate into cytokeratin 8 (CK8)-expressing epithelial progeny cells. Furthermore, RNA interference-mediated transient depletion of the tumor suppressor p53 followed by retrovirus-mediated transfer of c-Myc and K-Ras oncogenes in EpCAM-expressing ovarian stem-like cells resulted in the generation of ovarian T-ICs. The established ovarian T-ICs gave rise to hierarchically organized lethal tumors in vivo and were able to undergo peritoneal metastasis. Finally, subsequent RNA interference-mediated knockdown of p53 in tumor cells triggered the expansion of EpCAM-expressing stem-like tumor cells and induced further tumor growth. These data reveal a role for p53 in the development and expansion of ovarian stem-like tumor cells and subsequent malignant progression.
- Subjects
EPITHELIAL cells; CELL adhesion molecules; STEM cells; CANCER cells; TUMOR growth; DISEASE progression; KERATIN; GENE expression; CELLULAR signal transduction
- Publication
Carcinogenesis, 2011, Vol 32, Issue 11, p1597
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgr183