Document Detail


Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma.
MedLine Citation:
PMID:  22411819     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Identifying the cells of origin of lung cancer may lead to new therapeutic strategies. Previous work has focused upon the putative bronchoalveolar stem cell at the bronchioalveolar duct junction as a cancer cell of origin when a codon 12 K-Ras mutant is induced via adenoviral Cre inhalation. In the present study, we use two "knock-in" Cre-estrogen receptor alleles to inducibly express K-RasG12D in CC10(+) epithelial cells and Sftpc(+) type II alveolar cells of the adult mouse lung. Analysis of these mice identifies type II cells, Clara cells in the terminal bronchioles, and putative bronchoalveolar stem cells as cells of origin for K-Ras-induced lung hyperplasia. However, only type II cells appear to progress to adenocarcinoma.
Authors:
Xia Xu; Jason R Rock; Yun Lu; Christopher Futtner; Brian Schwab; Justin Guinney; Brigid L M Hogan; Mark W Onaitis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-12
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-28     Completed Date:  2012-05-21     Revised Date:  2013-12-08    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4910-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics,  metabolism*,  pathology*
Animals
Bronchioles / metabolism,  pathology
Cell Proliferation
Cell Transformation, Neoplastic / genetics,  pathology
Disease Progression
Gene Expression Regulation, Neoplastic
Green Fluorescent Proteins / metabolism
Hyperplasia
Lung Neoplasms / genetics,  metabolism*,  pathology*
Mice
Models, Biological
Mutant Proteins / metabolism
Oligonucleotide Array Sequence Analysis
Peptides / metabolism
Pneumocytes / metabolism*,  pathology*
Proto-Oncogene Proteins p21(ras) / genetics,  metabolism*
SOXB1 Transcription Factors / metabolism
Time Factors
Transcriptome / genetics
Uteroglobin / metabolism
Grant Support
ID/Acronym/Agency:
HL071303/HL/NHLBI NIH HHS; R01 HL071303/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Mutant Proteins; 0/Peptides; 0/SOXB1 Transcription Factors; 0/Scgb1a1 protein, mouse; 0/Sftpc protein, mouse; 0/Sox2 protein, mouse; 147336-22-9/Green Fluorescent Proteins; 9060-09-7/Uteroglobin; EC 3.6.5.2/Kras2 protein, mouse; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras)
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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