Journal Article

Transient depletion of p53 followed by transduction of c-Myc and K-Ras converts ovarian stem-like cells into tumor-initiating cells

Takeshi Motohara, Sachiko Masuko, Takatsugu Ishimoto, Toshifumi Yae, Nobuyuki Onishi, Teruyuki Muraguchi, Atsushi Hirao, Yumi Matsuzaki, Hironori Tashiro, Hidetaka Katabuchi, Hideyuki Saya and Osamu Nagano

in Carcinogenesis

Volume 32, issue 11, pages 1597-1606
Published in print November 2011 | ISSN: 0143-3334
Published online August 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgr183
Transient depletion of p53 followed by transduction of c-Myc and K-Ras converts ovarian stem-like cells into tumor-initiating cells

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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.

Journal Article.  6364 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.