Okamoto, A., Demetrick, D. J., Spillare, E. A., Hagiwara, K., Hussain, S. P., Bennett, W. P., Forrester, K., Gerwin, B., Serrano, M., Beach, D. H., Harris, C. C. (November 1994) Mutations and altered expression of p16INK4 in human cancer. Proceedings of the National Academy of Sciences of the United States of America, 91 (23). pp. 11045-11049. ISSN 0027-8424
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Abstract
Cell cycle arrest at the G(1) checkpoint allows completion of critical macromolecular events prior to S phase. Regulators of the G(1) checkpoint include an inhibitor of cyclin-dependent kinase, p16(INK4); two tumor-suppressor proteins, p53 and RB (the product of the retinoblastoma-susceptibility gene); and cyclin D1. Neither p16(INK4) nor the RB protein was detected in 28 of 29 tumor cell lines from human lung, esophagus, liver, colon, and pancreas. The presence of p16(INK4) protein is inversely correlated with detectable RB or cyclin D1 proteins and is not correlated with p53 mutations. Homozygous deletions of p16(INK4) were detected in several cell lines, but intragenic mutations of this gene were unusual in either cell lines or primary tumors. Transfection of the p16(INK4) cDNA expression vector into carcinoma cells inhibits their colony-forming efficiency and the p16(INK4) expressing cells are selected against with continued passage in vitro. These results are consistent with the hypothesis that p16(INK4) is a tumor-suppressor protein and that genetic and epigenetic abnormalities in genes controlling the G(1) checkpoint can lead to both escape from senescence and cancer formation.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | P53 PROTEIN TUMOR-SUPPRESSOR GENE CYCLIN D1 RETINOBLASTOMA PROTEIN D-TYPE CYCLINS RETINOBLASTOMA PROTEIN HOMOZYGOUS DELETIONS INTERFERON GENES BINDING PROTEIN CELL-LINES P53 GROWTH FIBROBLASTS OVEREXPRESSION |
| Subjects: | diseases & disorders > cancer organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle |
| CSHL Authors: | |
| Communities: | CSHL labs > Beach lab |
| Depositing User: | Matt Covey |
| Date: | November 1994 |
| Date Deposited: | 27 Aug 2015 19:15 |
| Last Modified: | 13 Sep 2019 16:44 |
| PMCID: | PMC45163 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31390 |
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