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.
Duke Scholars
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Related Subject Headings
- Tumor Suppressor Protein p53
- RNA, Messenger
- Mutation
- Methionine
- Immunoblotting
- Humans
- Heat-Shock Proteins
- Genes, p53
- Female
- Epitopes
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Suppressor Protein p53
- RNA, Messenger
- Mutation
- Methionine
- Immunoblotting
- Humans
- Heat-Shock Proteins
- Genes, p53
- Female
- Epitopes