BK virus as a cofactor in the etiology of prostate cancer in its early stages
BK virus as a cofactor in the etiology of prostate cancer in its early stages
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DOI：
10.1128/jvi.02461-07
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发表时间：
2008-03-01
影响因子：
5.4
通讯作者：
Imperiale, Michael J.
中科院分区：
文献类型：
--
作者：
Das, Dweepanita;Wojno, Kirk;Imperiale, Michael J.
2007年，前列腺癌预计会导致美国近10%的男性癌症死亡。与其他癌症相比，肿瘤抑制基因Rb1和P53的突变发生率较低，特别是在疾病的早期阶段。这导致了一种假设，即与人类病毒有关，如BK病毒(BKV)，它在尿路建立持续的亚临床感染，并编码干扰这些肿瘤抑制途径的癌蛋白。此前，我们在前列腺癌标本的良性和增生性炎性萎缩导管的上皮细胞中检测到BKV DNA。在本报告中，我们证明BKV在非癌前列腺癌中的出现频率要低得多。此外，在正常前列腺中，T抗原(TAG)仅在具有增生性炎性萎缩和前列腺上皮内瘤变的标本中观察到。我们进一步证明，表达TAG的萎缩细胞的P53基因是野生型的，而表达可检测到的核P53的肿瘤细胞含有野生型和突变型P53基因的混合，这表明TAG可能使萎缩细胞中的P53失活。我们的结果指向BKV在前列腺癌早期进展中的作用。
Prostate cancer has been projected to cause almost 10% of all male cancer deaths in the United States in 2007. The incidence of mutations in the tumor suppressor genes Rb1 and p53, especially in the early stages of the disease, is low compared to those for other cancers. This has led to the hypothesis that a human virus such as BK virus (BKV), which establishes a persistent subclinical infection in the urinary tract and encodes oncoproteins that interfere with these tumor suppressor pathways, is involved. Previously, we detected BKV DNA in the epithelial cells of benign and proliferative inflammatory atrophy ducts of cancerous prostate specimens. In the present report, we demonstrate that BKV is present at a much lower frequency in noncancerous prostates. Additionally, in normal prostates, T-antigen (TAg) expression is observed only in specimens harboring proliferative inflammatory atrophy and prostatic intraepithelial neoplasia. We further demonstrate that the p53 gene from atrophic cells expressing TAg is wild type, whereas tumor cells expressing detectable nuclear p53 contain a mix of wild-type and mutant p53 genes, suggesting that TAg may inactivate p53 in the atrophic cells. Our results point toward a role for BKV in early prostate cancer progression.