Endogenous p53 gene status predicts the response of human squamous cell carcinomas to wild-type p53.
Prior reports suggest that p53 protein status may influence the response to gene transduction with wild-type (wt) p53. Adenoviral vectors containing the p53 gene were administered to normal keratinocytes, to squamous cell carcinoma (SCC) lines with varied p53 protein status (absent, mutant, wt, or degraded by papillomavirus), as well as to tumors formed in severe combined immunodeficient mice. The percentage of cells undergoing apoptosis, G1 growth arrest, WAF1/p21 induction, and in vivo tumor progression were studied after wt p53 gene transduction. Apoptosis developed first in normal keratinocytes, next in SCCs lacking p53 protein, and last in SCCs with mutant or degraded p53 protein. All of the cell lines studied demonstrated an increase in WAF1/p21 protein, but only those lacking p53 protein showed G1 arrest. Tumors lacking p53 protein were more susceptible to p53 overexpression than those containing mutant or degraded p53 protein. The endogenous p53 protein status of SCCs appears to influence the outcome of p53 gene transduction.
St John
L S
LS
Department of Basic Sciences, Dental Branch, University of Texas-Houston Health Science Center, 77225, USA.
Sauter
E R
ER
Herlyn
M
M
Litwin
S
S
Adler-Storthz
K
K
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy*; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D016158:Genes, p53; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics; D011233:Precipitin Tests; D013997:Time Factors; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53