ANALYSIS OF THE ANTI-P53 ANTIBODY-RESPONSE IN CANCER-PATIENTS

Mutations in the p53 tumor suppressor gene giving rise to mutant p53 p roteins are among the most common genetic alterations associated with tumor cells. Mutant p53 gene products lose the wild type ability to su ppress transformation in vitro or regulate cellular gene transcription . Mutant and wild type p53 protein conformations differ and mutant p53 is often present at high levels in the tumor cell relative to the low levels found in normal cells. Despite the major advances made to char acterize the structure and biology of mutant and wild type p53, the hu moral immune response against mutant p53s remains to be clearly define d. In the present study we have examined the anti-p53 response from ca ncer patients against the native and denatured state of mutant and wil d type p53. Western blot analysis, immunoprecipitation analysis, and d ilution analysis demonstrate that the anti-p53 sera recognize both wil d type and mutant p53 conformational and denaturation resistant epitop es. There was no evidence that the mutant p53 molecules contain domina nt antigenic epitopes which are not present on the wild type p53 prote in. We also demonstrate that patients with ovarian cancer are also amo ng those which can produce anti-p53 antibodies.