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.
Footnotes
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↵1 This work was supported by Grant 3RT-022 from the University of California Tobacco-Related Disease Research Program and NIH Grant ES-05707 (to H. W.).
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↵2 To whom requests for reprints should be addressed, at Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, 9610 Medical Center Drive, Room 300, Rockville, Maryland 20850. Phone: (301) 402-3128; Fax: (301) 402-4422; E-mail: szaboe@bprb.nci.nih.gov.
- Received July 23, 1998.
- Accepted October 5, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 23
