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Paradoxical increase in retinoblastoma protein in colorectal carcinomas may protect cells from apoptosis.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 1999 Jul; Vol. 5 (7), pp. 1805-15. - Publication Year :
- 1999
-
Abstract
- The retinoblastoma (Rb) gene is inactivated in a variety of human cancers, but in colorectal carcinomas there is frequently increased expression of this gene. This is paradoxical in view of the known role of Rb as a tumor suppressor gene. In the present study, we compared the levels of expression of the Rb protein (pRb) in normal human colorectal mucosa, adenomatous polyps, and carcinomas by immunohistochemistry. In vitro studies were also done to examine the phenotypic effects of an antisense oligodeoxynucleotide (AS-Rb) targeted to Rb mRNA in the HCT116 colon carcinoma cell line that expresses a relatively high level of pRb. The incidence of pRb-positive cells was increased during multistage colorectal carcinogenesis. In vitro treatment of HCT116 cells with AS-Rb decreased the level of pRb by about 70% and also decreased the levels of the cyclin D1 protein and cyclin D1-associated kinase activity. AS-Rb inhibited growth of HCT116 cells and induced apoptosis. Reporter assays indicated about a 17-fold increase in E2F activity. These findings suggest that the increased expression of pRb in colorectal carcinoma cells may provide a homeostatic mechanism that protects them from growth inhibition and apoptosis, perhaps by counterbalancing potentially toxic effects of excessive E2F activity.
- Subjects :
- Cell Cycle
Cell Cycle Proteins metabolism
Cell Division genetics
Cell Size
Cells, Cultured
Colorectal Neoplasms pathology
E2F Transcription Factors
Humans
Immunohistochemistry
Oligonucleotides, Antisense genetics
Retinoblastoma Protein genetics
Retinoblastoma-Binding Protein 1
Transcription Factor DP1
Transcription Factors metabolism
Tumor Cells, Cultured
Apoptosis
Carrier Proteins
Colorectal Neoplasms metabolism
DNA-Binding Proteins
Retinoblastoma Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 5
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 10430085