Del Valle L, Baehring J, Lorenzana C, Giordano A, Khalili K, Croul S
The Center for NeuroVirology and Cancer Biology, Temple University, Philadelphia, PA 19122, USA.
Mol Pathol. 2001 Oct;54(5):331-7. doi: 10.1136/mp.54.5.331.
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.
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.
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.
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.
尽管髓母细胞瘤的病因仍不明确,但有几条证据表明其与嗜人神经的多瘤病毒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并使肿瘤抑制/细胞周期调节蛋白(如p53和视网膜母细胞瘤蛋白家族)失活的能力。
为了研究这些因素之间的潜在关系,采用免疫组织化学方法确定8例髓母细胞瘤中T抗原与p53以及视网膜母细胞瘤蛋白pRb、p107和Rb2/p130表达之间的关联。
仅3例表达T抗原的髓母细胞瘤对p53抗体也显示核阳性。尽管免疫组织化学在5例病例中检测到pRb的核标记,但3例T抗原阳性的病例显示出最高的pRb标记。视网膜母细胞瘤相关蛋白p107和Rb2/p130在大多数T抗原阳性的髓母细胞瘤中也呈免疫阳性。双重标记免疫组织化学还显示,在T抗原阳性的同一细胞中p53和pRb呈阳性。
这些相关性表明,在其中一些肿瘤中存在T抗原与p53和/或T抗原与pRb之间的关联。这些数据提供了间接证据,表明JC病毒通过T抗原可能参与了髓母细胞瘤的形成和进展。