Evidence that SOX2 overexpression is oncogenic in the lung.
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.


RESULTS
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.
Lu
Yun
Y
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
Futtner
Christopher
C
Rock
Jason R
JR
Xu
Xia
X
Whitworth
Walter
W
Hogan
Brigid L M
BL
Onaitis
Mark W
MW
D000818:Animals; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics*
D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse