title: Characterization of the cell of origin for small cell lung cancer.
abstract: Small cell lung carcinoma (SCLC) is a neuroendocrine subtype of lung cancer that affects more than 200,000 people worldwide every year with a very high mortality rate. Here, we used a mouse genetics approach to characterize the cell of origin for SCLC; in this mouse model, tumors are initiated by the deletion of the Rb and p53 tumor suppressor genes in the lung epithelium of adult mice. We found that mouse SCLCs often arise in the lung epithelium, where neuroendocrine cells are located, and that the majority of early lesions were composed of proliferating neuroendocrine cells. In addition, mice in which Rb and p53 are deleted in a variety of non-neuroendocrine lung epithelial cells did not develop SCLC. These data indicate that SCLC likely arises from neuroendocrine cells in the lung.
authors.affiliation: Department of Genetics, Stanford University, Palo Alto, CA, USA.
authors.forename: Kwon-Sik
authors.initials: KS
authors.lastname: Park
authors.forename: Mei-Chih
authors.initials: MC
authors.lastname: Liang
authors.forename: David M
authors.initials: DM
authors.lastname: Raiser
authors.forename: Raffaella
authors.initials: R
authors.lastname: Zamponi
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Roach
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Curtis
authors.forename: Zandra
authors.initials: Z
authors.lastname: Walton
authors.forename: Bethany E
authors.initials: BE
authors.lastname: Schaffer
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Roake
authors.forename: Anne-Flore
authors.initials: AF
authors.lastname: Zmoos
authors.forename: Christina
authors.initials: C
authors.lastname: Kriegel
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.forename: Julien
authors.initials: J
authors.lastname: Sage
authors.forename: Carla F
authors.initials: CF
authors.lastname: Kim
mesh_terms: D000818:Animals; D004848:Epithelium; D016161:Genes, Retinoblastoma / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D055099:Neuroendocrine Cells / Q000473:pathology*; D017384:Sequence Deletion; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53