title: MUC1 is a novel marker for the type II pneumocyte lineage during lung carcinogenesis.
abstract: Abnormalities in mucin-type glycoprotein expression have been documented in a variety of cancers, identifying these molecules as targets for immunologically based therapies and prognostic/diagnostic assays. We examined the expression of the membrane-bound MUC1 mucin in normal, histologically atypical, and neoplastic lung to determine its potential contribution to lung carcinogenesis. In vivo, intense MUC1 immunoreactivity was present in normal type II pneumocytes as well as in a range of atypical lesions derived from type II cells and >60% of primary and metastatic non-small cell lung cancers. Expression was not associated with altered survival, although it was highly correlated with the adenocarcinoma histology. A carcinogenesis model using 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone-exposed hamsters revealed that MUC1 mRNA increased prior to the histological appearance of tumors. In vitro studies using MUC1 expressing non-small cell lung cancer cell lines revealed that differentiation away from a type II cell lineage was associated with dramatic down-regulation of MUC1. We propose that MUC1 is a powerful new marker for the type II pneumocyte cell lineage that allows us to follow the type II pneumocyte lineage during the process of lung carcinogenesis.
authors.affiliation: Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Rockville, Maryland 20850, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Jarrard
authors.forename: R I
authors.initials: RI
authors.lastname: Linnoila
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: H
authors.initials: H
authors.lastname: Witschi
authors.forename: E
authors.initials: E
authors.lastname: Szabo
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002273:Carcinogens; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D006224:Cricetinae; D015536:Down-Regulation; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D008297:Male; D008647:Mesocricetus; D008875:Middle Aged; D018396:Mucin-1; D009602:Nitrosamines; D009842:Oligopeptides / Q000096:biosynthesis*; D010446:Peptide Fragments; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D056572:Histone Deacetylase Inhibitors; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D009602:Nitrosamines; D009842:Oligopeptides; D010446:Peptide Fragments; D012333:RNA, Messenger; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone