Role of the INK4a locus in tumor suppression and cell mortality

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:	Beach, David H.
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:	Publisher
URI:	https://repository.cshl.edu/id/eprint/30108

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