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Evidence that SOX2 overexpression is oncogenic in the lung.

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15.4 Mb
Date
2010-06-10
Authors
Lu, Y
Futtner, C
Rock, JR
Xu, X
Whitworth, W
Hogan, BL
Onaitis, MW
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4
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Abstract
BACKGROUND: SOX2 (Sry-box 2) is required to maintain a variety of stem cells, is overexpressed in some solid tumors, and is expressed in epithelial cells of the lung. METHODOLOGY/PRINCIPAL FINDINGS: We show that SOX2 is overexpressed in human squamous cell lung tumors and some adenocarcinomas. We have generated mouse models in which Sox2 is upregulated in epithelial cells of the lung during development and in the adult. In both cases, overexpression leads to extensive hyperplasia. In the terminal bronchioles, a trachea-like pseudostratified epithelium develops with p63-positive cells underlying columnar cells. Over 12-34 weeks, about half of the mice expressing the highest levels of Sox2 develop carcinoma. These tumors resemble adenocarcinoma but express the squamous marker, Trp63 (p63). CONCLUSIONS: These findings demonstrate that Sox2 overexpression both induces a proximal phenotype in the distal airways/alveoli and leads to cancer.
Type
Journal article
Subject
Animals
Immunohistochemistry
Lung
Lung Neoplasms
Mice
Mice, Transgenic
Models, Animal
Oncogenes
Polymerase Chain Reaction
SOXB1 Transcription Factors
Permalink
https://hdl.handle.net/10161/4546
Published Version (Please cite this version)
10.1371/journal.pone.0011022
Publication Info
Lu, Y; Futtner, C; Rock, JR; Xu, X; Whitworth, W; Hogan, BL; & Onaitis, MW (2010). Evidence that SOX2 overexpression is oncogenic in the lung. PLoS One, 5(6). pp. e11022. 10.1371/journal.pone.0011022. Retrieved from https://hdl.handle.net/10161/4546.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Hogan

Brigid L. M. Hogan

Research Professor of Cell Biology
1. Genetic regulation of embryo development using the mouse as a research model. 2. The role of genes and signaling pathways in directing and co-ordinating the development of the lung. 3. The identity and regulation of the different stem cells in the adult lung and their role in repair, fibrosis and cancer.
Onaitis

Mark William Onaitis

Adjunct Associate Professor in the Department of Surgery
Mouse Models of Foregut Malignancies Normal Tissue and Cancer Stem Cells Risk Prediction in Thoracic Malignancies
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