The role of CC10 in pulmonary carcinogenesis: from a marker to tumor suppression.
CC10 is infrequently expressed in human non-small cell lung cancers (NSCLCs), despite being abundantly produced by progenitor cells for normal and neoplastic epithelium. Many abnormalities in the surrounding lung associated with field carcinogenesis, which reflect prolonged exposure to such carcinogens as tobacco smoke, also revealed altered expression of CC10. Exposure of hamsters and mice to the tobacco-specific carcinogen NNK led to reduced CC10 expression, which was partially reversible. Overexpression of CC10 in immortalized bronchial epithelial cells delayed the induction of anchorage-independent growth in response to NNK. The data suggest that downregulation of CC10 contributes to carcinogenesis because CC10 antagonizes the neoplastic phenotype.
Linnoila
R I
RI
Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, 9610 Medical Center Drive, Suite 300, Rockville, MD 20850, USA. ill7h@nih.gov
Szabo
E
E
DeMayo
F
F
Witschi
H
H
Sabourin
C
C
Malkinson
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014598:Uteroglobin
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011506:Proteins; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; D016708:Synaptophysin; D014598:Uteroglobin