Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers.
Davidoff, A M, et al.
Proc. Natl. Acad. Sci. U.S.A., 89: 3439-42 (1992)
1992
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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. | 1373500
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p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines.
Lehman, T A, et al.
Cancer Res., 51: 4090-6 (1991)
1991
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The p53 tumor suppressor gene is frequently mutated and the K-ras oncogene is occasionally mutated in primary specimens of human lung carcinomas. These mutated genes also cooperate in the immortalization and neoplastic transformation of rodent cells. To determine whether these mutations are necessary for maintenance of the immortalized and/or neoplastically transformed states of human bronchial epithelial cells, the p53 gene and regions of the ras (K-, H-, and N-) genes were sequenced in nine human lung carcinoma cell lines. Detection of p53 mutations by polymerase chain amplification and direct DNA sequencing was corroborated by p53 immunocytochemistry and coimmunoprecipitation of p53 with heat shock protein 70. p53 and ras genes were frequently, but not always, mutated in the carcinoma cell lines. These data are consistent with the hypothesis that multiple genetic changes involving both protooncogenes and tumor suppressor genes occur during lung carcinogenesis. | 1855224
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Monoclonal antibodies specific for simian virus 40 tumor antigens.
Harlow, E, et al.
J. Virol., 39: 861-9 (1981)
1981
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Thirty hybridomas that secrete immunoglobulins against the simian virus 40 tumor antigens were isolated and cloned. Of these, 28 produced antibodies which bound to simian virus 40 large-T, and 2 produced antibodies which bound to the host 53,000-dalton protein. As in previous work, large-T antigen was found to have at least one determinant that it shared with small-t antigen and to have a minimum of six unique determinants. Several of the monoclonal antibodies from the L series hybridomas recognized determinants that were present on a subset of the large-T antigen from simian virus 40-transformed mouse cells. These monoclonal antibodies should be useful in studies of the structure and function of the simian virus 40 tumor antigens. | 6169844
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