Abstract
The p16INK4 (MTS1) gene has many features of a tumor suppressor gene. It maps to 9p21, a region of frequent loss of heterozygosity in a variety of tumor types. It encodes an inhibitor of cyclin-dependent kinase 4, and its homozygous deletion is common in tumor-derived cell lines. To examine its tumor suppressive function and its potential in cancer gene replacement therapy, wild-type p16INK4 was expressed in an adenovirus-derived gene delivery system and introduced into lung cancer cell lines that do not express p16INK4. Expression of the introduced p16INK4 blocked tumor cell entry into S phase of the cell cycle and inhibited tumor proliferation both in vitro and in vivo. These observations strongly support that p16INK4 is a tumor suppressor gene and is a candidate for cancer gene replacement therapy.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adenoviridae / genetics*
-
Animals
-
Base Sequence
-
Carcinoma, Non-Small-Cell Lung / metabolism*
-
Carcinoma, Non-Small-Cell Lung / therapy
-
Carcinoma, Non-Small-Cell Lung / virology
-
Carrier Proteins / genetics
-
Carrier Proteins / metabolism*
-
Carrier Proteins / physiology
-
Cell Cycle / genetics*
-
Cell Division / genetics
-
Cyclin-Dependent Kinase Inhibitor p16
-
Cyclin-Dependent Kinases / metabolism
-
Gene Deletion
-
Genes, Tumor Suppressor / physiology*
-
Genetic Vectors / physiology*
-
Humans
-
Lung Neoplasms / metabolism*
-
Lung Neoplasms / therapy
-
Lung Neoplasms / virology
-
Mice
-
Mice, Inbred BALB C
-
Mice, Nude
-
Molecular Sequence Data
-
Transfection / methods
-
Tumor Cells, Cultured
Substances
-
Carrier Proteins
-
Cyclin-Dependent Kinase Inhibitor p16
-
Cyclin-Dependent Kinases