| Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues |
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| Author(s): Hochedlinger K, Yamada Y, Beard C, Jaenisch R |
| Source: CELL Volume: 121 Issue: 3 Pages: 465-477 Published: MAY 6 2005 |
| Times Cited: 139 References: 83 |
| Abstract: The POU-domain transcription factor Oct-4 is normally expressed in pluripotent cells of the mammalian embryo. In addition, germ-cell tumors and a few somatic tumors show detectable expression of Oct-4. While Oct-4's role during preimplantation development is to maintain embryonic cells in a pluripotent state, little is known about its potential oncogenic properties. Here we investigate the effect of ectopic Oct-4 expression on somatic tissues of adult mice using a doxycycline-dependent expression system. Activation of Oct-4 results in dysplastic growths in epithelial tissues that are dependent on continuous Oct-4 expression. Dysplastic lesions show an expansion of progenitor cells and increased β-catenin transcriptional activity. In the intestine, Oct-4 expression causes dysplasia by inhibiting cellular differentiation in a manner similar to that in embryonic cells. These data show that certain adult progenitors remain competent to interpret key embryonic signals and support the notion that progenitor cells are a driving force in tumorigenesis. |
| Document Type: Article |
| Language: English |
| Reprint Address: Jaenisch, R (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA |
Addresses:
1. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
2. MIT, Dept Biol, Cambridge, MA 02141 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 925DL |
| ISSN: 0092-8674 |
| DOI: 10.1016/j.cell.2005.02.018 |