Expression of a human polyomavirus oncoprotein and tumour suppressor proteins in medulloblastomas

Expression of a human polyomavirus oncoprotein and tumour suppressor proteins in medulloblastomas
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DOI:
10.1136/mp.54.5.331
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发表时间:
2001-10-01
期刊:
JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY
影响因子:
--
通讯作者:
Croul, S
Croul, S
中科院分区:
其他
文献类型:
--
作者:
Del Valle, L;Baehring, J;Croul, S

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目的:虽然髓母细胞瘤的病因仍不清楚,但有几条证据表明与人类嗜神经性多瘤病毒JC及其癌蛋白T抗原有关。JC病毒T抗原的致瘤特性至少部分是由于其结合和失活肿瘤抑制因子/细胞周期调节蛋白如P53和视网膜母细胞瘤蛋白家族的能力所致。方法:采用免疫组织化学方法检测8例髓母细胞瘤中T抗原和P53蛋白表达与Rb2/p130蛋白表达的关系。结果:仅3例T抗原表达的髓母细胞瘤与P53抗体阳性。虽然免疫组织化学检测到5例pRb的核标记,但T抗原阳性的3例pRb的标记率最高。在大多数T抗原阳性的髓母细胞瘤中,视网膜母细胞瘤相关蛋白p107和Rb2/p130也呈免疫阳性。双标免疫组织化学也显示T抗原阳性的肿瘤细胞中P53和pRb阳性。结论:T抗原与P53和/或T抗原与pRb在某些肿瘤中存在关联。这些数据提供了间接证据,表明JC病毒通过T抗原作用于髓母细胞瘤的形成和发展。
Aims-Although the aetiology of medulloblastoma remains elusive, several lines of evidence suggest an association with the human neurotropic polyomavirus JC and its oncoprotein T antigen. The tumour forming properties of JC virus T antigen are the result, at least in part, of its ability to bind and inactivate tumour suppressor/ cell cycle regulatory proteins, such as p53 and the retinoblastoma family of proteins.Methods-To examine potential relations between these factors, immunohistochemistry was used to determine associations between the T antigen and the expression of p53 and the retinoblastoma proteins pRb, p107, and Rb2/p130 in eight medulloblastomas.Results-Only the three medulloblastomas with T antigen expression also showed nuclear positivity with antibodies to p53. Although immunohistochemistry detected nuclear labelling for pRb in five of the cases, the three that were positive for T antigen showed the highest pRb labelling. The retinoblastoma related proteins p107 and Rb2/p130 were also immunopositive in most T antigen positive medulloblastomas. Double label immunohistochemistry also demonstrated p53 and pRb positivity in the same cells that were T antigen positive.Conclusions-These correlations suggest that associations between T antigen and p53 and/or T antigen and pRb occur in some of these tumours. These data provide indirect evidence that JC virus, acting through T antigen, might be involved in the formation and progression of medulloblastoma.