title: Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma.
abstract: 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.affiliation: Department of Surgery, Duke University, Durham, NC 27710, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Jason R
authors.initials: JR
authors.lastname: Rock
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.forename: Christopher
authors.initials: C
authors.lastname: Futtner
authors.forename: Brian
authors.initials: B
authors.lastname: Schwab
authors.forename: Justin
authors.initials: J
authors.lastname: Guinney
authors.forename: Brigid L M
authors.initials: BL
authors.lastname: Hogan
authors.forename: Mark W
authors.initials: MW
authors.lastname: Onaitis
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D056809:Alveolar Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D055745:Bronchioles / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006965:Hyperplasia; D036341:Intercellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D037721:Pulmonary Surfactant-Associated Protein C; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013997:Time Factors; D059467:Transcriptome / Q000235:genetics; D014598:Uteroglobin / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D010455:Peptides; D037721:Pulmonary Surfactant-Associated Protein C; D055748:SOXB1 Transcription Factors; C556390:Scgb1a1 protein, mouse; C489680:Sftpc protein, mouse; C527783:Sox2 protein, mouse; D049452:Green Fluorescent Proteins; D014598:Uteroglobin; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)