Restoration of p53 functions suppresses tumor growth of pancreatic cells with different p53 status.
Pancreatic tumor cells show a very high frequency of p53 mutation. Our aim in this study was to determine if the restoration of wild-type p53 function could be used to eliminate the tumorigenic phenotype in these cells. Pancreatic tumor cell lines, CRL1420, which contains elevated levels of mutant p53, and CRL1682, with no detectable p53 protein, were stably transfected with the exogenous wild-type p53 gene. The growth rate and tumorigenicity in nude mice of wild-type p53 expressing clones were measured. Our data showed that the expression of wild-type p53 decreased the growth rate of CRL1420 and completely suppressed its potential for tumor formation in nude mice. Moreover, the size of the tumor formed in nude mice by CRL1682 was reduced drastically. G1 arrest as a possible cause for tumor suppression was investigated by flowcytometry. Neither of the cell lines irrespective of the status of p53 was arrested at G1 in response to x-irradiation. Thus, our results provide functional evidence that the deletion or mutational inactivation of the p53 gene represents an important step in the tumorigenicity of pancreatic cancer. Furthermore, the extent of the restoration of p53 function by introduction of the p53 gene depends on both the cell type and the cell settings (in vitro or in vivo conditions).
Taghavi
Marzieh H S
MH
Ministry of Science, Tehran, Iran. mtaghavi_ca@yahoo.com
Davoodi
Jamshid
J
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D017353:Gene Deletion; D017930:Genes, Reporter; D006801:Humans; D019868:Kanamycin Kinase / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D019868:Kanamycin Kinase