p21(WAF1/Cip1) retards the growth of human squamous cell carcinomas in vivo.
The excessive proliferation exhibited by cancer cells is frequently a result of their failure to adequately regulate cell cycle progression. In the present study, we developed a xenograft model of oral cancer in athymic mice, using squamous carcinoma cell lines and examined the ability of the cyclin-dependent kinase inhibitor p21 (WAF1/Cip1) to retard tumour growth in vivo, using a retroviral delivery system. Human p21 cDNA was cloned by polymerase chain reaction, expressed, and the encoded protein shown to have biological activity in in vitro kinase assays. Amphotropic retrovirus cultures which expressed recombinant p21 were generated and used to treat established squamous cell carcinoma xenografts. Two weeks following onset of treatment tumours injected with p21 virus producer cells showed a reduction in size between 3- and 10-fold compared with tumours which received control cells which produced control virus alone. The data indicate that recombinant p21 may be of future use for therapeutic intervention in oral cancer.
Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, Bethesda, MD 20892-4330, USA. cardinali@a1.cber.fda.gov
M
M
Cardinali
J
J
Jakus
S
S
Shah
J F
JF
Ensley
K C
KC
Robbins
W A
WA
Yeudall
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009368:Neoplasm Transplantation; D012190:Retroviridae / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins