Overexpression of human p21waf1/cip1 arrests the growth of chicken embryo fibroblasts transformed by individual oncogenes.
In normal cells, cell growth and division is controlled by the interplay between proto-oncogenes and tumor suppressor genes. Cancer cells usually have both activated an oncogene and have lost a functional tumor suppressor gene. High level expression of a tumor suppressor, p53, can block the growth of cancer cells. waf1/cip1 is transactivated by the tumor suppressor p53 and the p21waf1/cip1 protein is itself a suppressor of cell growth. To test the effect of growth suppression genes on the growth of cells transformed by individual oncogenes, we have used replication-competent retroviral vectors to induce high level expression of p53 and p21waf1/cip1. Overexpression of p21waf1/cip1 arrests the growth of chicken embryo fibroblasts (CEF) transformed by v-Src, tf-Ras, c-Mos and c-Myc. These data suggest that p21waf1/cip1 might be a useful tool in gene therapy for human cancer.
Givol
I
I
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Givol
D
D
Rulong
S
S
Resau
J
J
Tsarfaty
I
I
Hughes
S H
SH
D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002642:Chick Embryo; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D004791:Enzyme Inhibitors; D016193:G1 Phase; D006801:Humans; D009857:Oncogenes; D011817:Rabbits; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53