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Molecular pathology of the cell cycle in human cancer cells
J Bártek1, Z Stasková, G Draetta
1Department of Tumour Biology, Institute of Haematology and Blood Transfusion, Prague, Czech Republic.
Abstract:
Recent evidence from molecular biology studies of the cell cycle machinery suggests that, apart from oncogenes and tumor suppressor genes, the genes encoding the key cell cycle regulatory proteins could serve as additional targets for oncogenic mutations involved in the multistep process of carcinogenesis. In an attempt to identify such potential cancer-associated aberrations of the cell cycle regulators, the expression of cdc2 and cdk2 kinases, as well as cyclins A, B1 and D1, was analyzed by immunoblotting in a panel of more than 40 human cancer cell lines derived from 17 different tumor types. The expression of cdc2, cdk2, cyclin B1 and cyclin A polypeptides was detectable in all lines examined, and moderate variation in protein level does not provide evidence for any obvious abnormalities in the cancer cell lines studied. The application of a series of novel monoclonal antibodies (Mab) to human cdc2 revealed the existence of an intriguing protein, designated p37, immunologically and structurally related to cdc2, which is strongly and selectively expressed in about 50% of the cancer cell lines. In contrast to cyclin A, which has also been implicated in tumorigenesis, we found pronounced variation in abundance of the cyclin D1 protein. Our data suggest that dysregulation of cyclin D1 (a candidate bcl-1, PRAD1 oncogene) can be involved in the pathogenesis of some additional tumor types (e.g., sarcomas and neuroblastomas) besides those reported for amplification and/or mRNA overexpression of this oncogene.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Cell cycle regulators like cyclin D1 may be mutated in cancer. Researchers found dysregulation of cyclin D1 in various cancer cell lines, suggesting its role in carcinogenesis beyond known oncogenes.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Cycle Regulation
Background:
- Cell cycle machinery genes are potential targets for oncogenic mutations in carcinogenesis.
- Understanding aberrations in cell cycle regulators is crucial for cancer research.
Purpose of the Study:
- To identify cancer-associated aberrations in key cell cycle regulatory proteins.
- To analyze the expression of cdc2, cdk2, cyclins A, B1, and D1 in human cancer cell lines.
Main Methods:
- Immunoblotting analysis of cell cycle regulator expression.
- Utilized novel monoclonal antibodies against human cdc2.
- Examined over 40 human cancer cell lines from 17 tumor types.
Main Results:
- Expression of cdc2, cdk2, cyclin B1, and cyclin A was detected in all cell lines with moderate variation.
- A novel cdc2-related protein, p37, was selectively expressed in approximately 50% of cancer cell lines.
- Pronounced variation in cyclin D1 protein abundance was observed, suggesting its dysregulation in various cancers.
Conclusions:
- Dysregulation of cyclin D1 may contribute to the pathogenesis of additional tumor types, including sarcomas and neuroblastomas.
- Cell cycle regulators, beyond known oncogenes and tumor suppressors, are critical targets in cancer development.