IMMUNE-RESPONSE TO P53 IS DEPENDENT UPON P53/HSP70 COMPLEXES IN BREAST CANCERS
IMMUNE-RESPONSE TO P53 IS DEPENDENT UPON P53/HSP70 COMPLEXES IN BREAST CANCERS
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DOI：
10.1073/pnas.89.8.3439
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发表时间：
1992-04-15
影响因子：
11.1
通讯作者：
MARKS, JR
中科院分区：
文献类型：
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作者：
DAVIDOFF, AM;IGLEHART, JD;MARKS, JR
在> 25%的原发性人类乳腺癌中检测到p53蛋白的过度表达，这是由增加蛋白稳定性的基因突变引起的。此外，几乎等于10%的乳腺癌患者具有针对p53蛋白的循环抗体。在这项研究中，抗p53体液反应与肿瘤中表达的突变型p53蛋白的存在和类型相关。在一系列的60例乳腺癌患者中，30例正常的低水平p53表达的肿瘤中0例诱导抗p53抗体，而30例p53过表达的肿瘤中7例（23%）引起特异性抗p53抗体应答。这7例患者具有识别野生型p53和多种突变型p53蛋白的抗p53抗体。p53突变的比较显示抗体阴性肿瘤仅在外显子7和8中具有突变，而抗体阳性肿瘤主要在外显子5和6中具有突变。此外，所有引发抗体的肿瘤都含有p53和70 kDa热休克蛋白之间的复合物，而抗体阴性肿瘤都不含有这种复合物。这项研究暗示了70 kDa的热休克蛋白在p53的抗原呈递。
Overexpression of the p53 protein, resulting from gene mutations that increase protein stability, has been detected in > 25% of primary human breast cancers. In addition, almost-equal-to 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.