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Dysregulated Expression of Stem Cell Factor Bmi1 in Precancerous Lesions of the Gastrointestinal Tract
- Source :
- Clinical Cancer Research. 12:6960-6966
- Publication Year :
- 2006
- Publisher :
- American Association for Cancer Research (AACR), 2006.
-
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, β-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.
- Subjects :
- Senescence
Cancer Research
Pathology
medicine.medical_specialty
Colon
macromolecular substances
Polymerase Chain Reaction
Malignant transformation
GLI1
Cell Line, Tumor
Proto-Oncogene Proteins
Gene expression
medicine
Humans
Hedgehog Proteins
RNA, Messenger
Promoter Regions, Genetic
Cyclin-Dependent Kinase Inhibitor p16
Gastrointestinal Neoplasms
Polycomb Repressive Complex 1
Gastrointestinal tract
biology
Gene Expression Profiling
Nuclear Proteins
Cancer
DNA Methylation
medicine.disease
female genital diseases and pregnancy complications
Gastrointestinal Tract
Gene Expression Regulation, Neoplastic
Repressor Proteins
Wnt Proteins
Oncology
Dysplasia
BMI1
Colonic Neoplasms
biology.protein
Cancer research
Precancerous Conditions
Signal Transduction
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....96f8f6449bbd0424ca26ab556a0c6317