Serrano, M., Lee, H., Chin, L., Cordon-Cardo, C., Beach, D., DePinho, R. A.
(April 1996)
Role of the INK4a locus in tumor suppression and cell mortality.
Cell, 85 (1).
pp. 27-37.
ISSN 0092-8674 (Print)
Abstract
The cell cycle inhibitor p16INK4a is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer. Tumor-associated alterations in the INK4a locus may also affect the overlapping gene encoding p19ARF and the adjacent gene encoding p15I1NK4b, both negative regulators of cell proliferation. We report the phenotype of mice carrying a targeted deletion of the INK4a locus that eliminates both p16INK4a and p19ARF. The mice are viable but develop spontaneous tumors at an early age and are highly sensitive to carcinogenic treatments. INK4a-deficient primary fibroblasts proliferate rapidly and have a high colony-formation efficiency. In contrast with normal cells, the introduction of activated Ha-ras into INK4a-deficient fibroblasts can result in neoplastic transformation. These findings directly demonstrate that the INK4a locus functions to suppress neoplastic growth.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
Alleles
Animals
Carrier Proteins/ genetics
Cell Death/genetics
Cell Division/genetics
Cell Transformation, Neoplastic
Cyclin-Dependent Kinase Inhibitor p16
Enzyme Inhibitors
Fibroblasts/chemistry/physiology
Genes, Tumor Suppressor/ physiology
Germ-Line Mutation/physiology
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Phenotype
Proteins/genetics
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Tumor Suppressor Protein p14ARF |
| Subjects: |
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell death
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell division
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Beach lab |
| Depositing User: |
Kathleen Darby
|
| Date: |
5 April 1996 |
| Date Deposited: |
12 May 2014 17:39 |
| Last Modified: |
12 May 2014 17:39 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/30108 |
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