RRC ID 42829
Author Tateishi K, Ohta M, Kanai F, Guleng B, Tanaka Y, Asaoka Y, Tada M, Seto M, Jazag A, Lianjie L, Okamoto M, Isayama H, Tada M, Yoshida H, Kawabe T, Omata M.
Title Dysregulated expression of stem cell factor Bmi1 in precancerous lesions of the gastrointestinal tract.
Journal Clin Cancer Res
Abstract PURPOSE:It is important to identify the definitive molecular switches involved in the malignant transformation of premalignant tissues. Cellular senescence is a specific characteristic of precancerous tissues, but not of cancers, which might reflect tumorigenesis-protecting mechanisms in premalignant lesions. Polycomb protein Bmi1, which is a potent negative regulator of the p16INK4 gene, suppresses senescence in primary cells and is overexpressed in various cancers. We hypothesized that Bmi1 expression would also be dysregulated in precancerous lesions in human digestive precancerous tissues.
EXPERIMENTAL DESIGN:Bmi1 expression was investigated in cancerous and precancerous tissues of the digestive tract. The expression of p16, beta-catenin, and Gli1 and the in vivo methylation status of the p16 gene were also analyzed in serial sections of colonic precancerous lesions.
RESULTS:Bmi1 was clearly overexpressed across a broad spectrum of gastrointestinal cancers, and the expression of Bmi1 increased in a manner that reflected the pathologic malignant features of precancerous colonic tissues (low-grade dysplasia, 12.9 +/- 2.0%; high-grade dysplasia, 82.9 +/- 1.6%; cancer, 87.5 +/- 2.4%). p16 was also strongly expressed in high-grade dysplasia, but not in cancers. p16 promoter methylation was detected only in some Bmi1-positive neoplastic cells.
CONCLUSIONS:Bmi1 overexpression was correlated with the malignant grades of human digestive precancerous tissues, which suggests that advanced Bmi1 dysregulation might predict malignant progression. The abnormal Bmi1 expression might link to malignant transformation via the disturbance of orderly histone modification.
Volume 12(23)
Pages 6960-6
Published 2006-12-1
DOI 10.1158/1078-0432.CCR-06-0449
PII 12/23/6960
PMID 17145814
MeSH Cell Line, Tumor Colon / metabolism Colon / pathology Colonic Neoplasms / genetics* Colonic Neoplasms / metabolism Colonic Neoplasms / pathology Cyclin-Dependent Kinase Inhibitor p16 / genetics Cyclin-Dependent Kinase Inhibitor p16 / metabolism DNA Methylation Gastrointestinal Neoplasms / genetics* Gastrointestinal Neoplasms / metabolism Gastrointestinal Neoplasms / pathology Gastrointestinal Tract / metabolism Gastrointestinal Tract / pathology* Gene Expression Profiling Gene Expression Regulation, Neoplastic / genetics* Hedgehog Proteins / metabolism Humans Nuclear Proteins / genetics* Nuclear Proteins / metabolism Polycomb Repressive Complex 1 Polymerase Chain Reaction / methods Precancerous Conditions / genetics* Precancerous Conditions / pathology Promoter Regions, Genetic / genetics Proto-Oncogene Proteins / genetics* Proto-Oncogene Proteins / metabolism RNA, Messenger / biosynthesis RNA, Messenger / genetics Repressor Proteins / genetics* Repressor Proteins / metabolism Signal Transduction / genetics Wnt Proteins / metabolism
IF 10.107
Times Cited 51
Human and Animal Cells 293T(RCB2202)