Sensitivity to cisplatin treatment of human K1 thyroid carcinoma cell lines with altered p53 function.
OBJECTIVE
p53 is the most frequently altered gene in human cancer. It was expected to be the principle marker for chemo/radiosensitivity, resistance, tumor recurrence and ultimate survival, but is no longer considered a universal prognostic factor. Different alterations in the p53 gene have led to conflicting results depending on cell/tissue specificities and on radiation and drug specificities.


METHODS
We evaluated the properties of isogenic and isophenotypic cell lines from the K1 papillary thyroid carcinoma in which p53 function was disrupted either by mutation (expression of dominant-negative p53, 143(ala)) or by inactivation (expression of human papilloma virus protein HPV16 E6). Their proliferation, their propensity to trigger apoptosis and their survival were analyzed after treatment with cisplatin (CDDP).


RESULTS
Only K1 lines with wild-type p53 had significantly accumulated apoptotic bodies 72 h after treatment. Despite their incapacity to trigger apoptosis in response to CDDP treatment, the survival of K1 cell lines in which p53 expression was altered was not significantly different from the survival of K1 cell lines expressing wild-type p53. In addition, the order of magnitude of resistance of K1 cells in which p53 was mutated was similar to that in which p53 was totally inactivated, although the pathways involved may be different.


CONCLUSIONS
These results show that the means by which p53 expression is disrupted and the consequence on downstream pathways regulated by p53 deserve to be considered in order to elucidate some apparently conflicting responses of this gene.
Céraline
Jocelyn
J
Altérations Génétiques des Cancers et Réponse Thérapeutique, UPRES-EA 3430, Laboratoire de Cancérologie Expérimentale et de Radiobiologie, Institut de Recherche contre les Cancers de l'Appareil Digestif, Hôpitaux Universitaires de Strasbourg, France.
Deplanque
Gaël
G
Noël
Francine
F
Natarajan-Amé
Shanti
S
Bergerat
Jean-Pierre
JP
Klein-Soyer
Claudine
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D006801:Humans; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin