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 beta-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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Differentiation / genetics*
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Cell Lineage / genetics
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Doxycycline / administration & dosage
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Doxycycline / toxicity
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Epithelium / metabolism
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Epithelium / pathology*
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Gastrointestinal Tract / drug effects
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Gastrointestinal Tract / metabolism
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Gastrointestinal Tract / pathology
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Gene Expression / drug effects
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Gene Expression / genetics
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Green Fluorescent Proteins / genetics
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Intestinal Mucosa / metabolism
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Intestines / drug effects
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Intestines / pathology
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Mice
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Mice, Transgenic
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Neoplasms / etiology
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Neoplasms / genetics
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Neoplasms / pathology
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Octamer Transcription Factor-3
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Skin / drug effects
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Skin / metabolism
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Skin / pathology
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Stem Cells / metabolism
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Stem Cells / pathology*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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beta Catenin
Substances
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CTNNB1 protein, mouse
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Octamer Transcription Factor-3
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Pou5f1 protein, mouse
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Trans-Activators
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Transcription Factors
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beta Catenin
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Green Fluorescent Proteins
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Doxycycline