Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers.
Overexpression of the p53 protein, resulting from gene mutations that increase protein stability, has been detected in greater than 25% of primary human breast cancers. In addition, approximately 10% of breast cancer patients have circulating antibodies to the p53 protein. In this study, the anti-p53 humoral response is correlated with the presence and type of mutant p53 protein expressed in the tumor. In a series of 60 breast cancer patients, 0 of 30 tumors with normal, low-level p53 expression induced anti-p53 antibodies, whereas 7 (23%) of 30 tumors with p53 overexpression elicited a specific anti-p53 antibody response. These 7 patients had anti-p53 antibodies that recognized wild-type p53 and a variety of mutant p53 proteins. A comparison of p53 mutations revealed that antibody-negative tumors had mutations exclusively in exons 7 and 8, whereas antibody-positive tumors had mutations primarily in exons 5 and 6. Moreover, all antibody-eliciting tumors contained complexes between p53 and a 70-kDa heat shock protein, whereas none of the antibody-negative tumors contained this complex. This study implicates a 70-kDa heat shock protein in the antigenic presentation of p53.
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
A M
AM
Davidoff
J D
JD
Iglehart
J R
JR
Marks
D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D002460:Cell Line; D003062:Codon; D000939:Epitopes / Q000032:analysis; D005260:Female; D016158:Genes, p53; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008715:Methionine / Q000378:metabolism; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003062:Codon; D000939:Epitopes; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D008715:Methionine