Korean J Intern Med.  1999 Jan;14(1):53-58.

The effects of transferring tumor suppressor gene p16INK4A to p16INK4A-deleted cancer cells

• Lee KY
• Yoo CG
• Han SK
• Shim YS
• Kim YW

Abstract

OBJECTIVES
p16 is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressive gene 1). Especially in the case of non-small cell lung cancer, it was not expressed in more than 70% of cell lines examined. To determine changes in cell-cycle related proteins and the tumorigenic effect, we, therefore, transfected p16INK4A gene into lung cancer cell lines. METHODS: We transfected p16INK4A gene into lung cancer cell lines which do not express p16 protein. We evaluated the effect by clonogenic assay and observed the changes of cell-cycle related proteins. RESULTS: The newly-expressed p16 formed a complex with cdk4, and phosphorylated pRB was decreased, although cyclin D1 and pRB:cyclin D1 complex were unchanged. Clonogenic assay after selection with G418 showed that, in the cell lines transfected with p16, tumorigenicity was significantly less than in the control. CONCLUSION: These results suggest that the p16INK4A gene can be a candidate for gene therapy in cases of NSCLC in which p16INK4A gene is inactivated.

Keyword

p16(INK4A); lung cancer; gene therapy; cell cycle

MeSH Terms

Carcinoma, Non-Small-Cell Lung/therapy
Carcinoma, Non-Small-Cell Lung/genetics
Cyclins/metabolism
Gene Deletion
Gene Therapy
Genes, p16*
Human
Lung Neoplasms/therapy*
Lung Neoplasms/metabolism
Lung Neoplasms/genetics*
Nuclear Proteins/metabolism
Support, Non-U.S. Gov't
Transfection
Tumor Cells, Cultured