Chronic bacterial inflammation induces prostatic intraepithelial neoplasia in mouse prostate.
Chronic bacterial inflammation induces prostatic intraepithelial neoplasia in mouse prostate.
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DOI：
10.1038/sj.bjc.6605370
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发表时间：
2009-11-17
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管前列腺癌的病因仍不清楚，但我们假设慢性细菌损伤在前列腺癌发生中起主要作用。感染磷酸盐缓冲盐水或大肠杆菌的雄性 C3H/HeOuJ 小鼠在第 5 天、第 12 周或第 26 周时被处死。评估收获的前列腺组织的炎症反应并针对肿瘤转化标记物进行免疫染色。所有受感染的小鼠均出现细菌性前列腺炎。对照小鼠没有前列腺感染或炎症。感染5天的小鼠在前列腺腺腔内出现急性炎症灶，伴有中性粒细胞浸润和上皮坏死碎片。所有感染 12 周的小鼠都有慢性炎症的证据，基质中有致密的炎症浸润。前列腺上皮表现出不同程度的不典型增生，上皮细胞层数增多，细胞学异型性。 26周时，不典型增生变化更加明显，类似于前列腺上皮内瘤变和高度不典型增生。与对照前列腺相比，表现出反应性发育不良的前列腺的氧化 DNA 损伤染色更强，上皮细胞增殖增加，雄激素受体、GSTP1、p27Kip1 和 PTEN 表达减少。这些数据表明，慢性炎症会诱发局灶性前列腺腺体异型性，并表明炎症与前列腺瘤形成之间存在潜在联系。
Although the aetiology of prostate cancer remains unknown, we hypothesised that chronic bacterial insult has a major role in prostate carcinogenesis. Male C3H/HeOuJ mice, infected with phosphate-buffered saline or Escherichia coli bacteria, were killed at 5 days, or at 12 or 26 weeks. Harvested prostate tissues were evaluated for inflammatory responses and immunostained for neoplastic transformation markers. All infected mice developed bacterial prostatitis. Control mice had no prostate infections or inflammation. Mice infected for 5 days showed foci of acute inflammation with infiltrating neutrophils and epithelial necrotic debris in the prostatic glandular lumen. All mice infected for 12 weeks had evidence of chronic inflammation with dense inflammatory infiltrates in the stroma. The prostatic epithelium showed varying degrees of atypical hyperplasia with increased epithelial cell layers and cytological atypia. At 26 weeks, the dysplastic changes were more pronounced and mimicked a prostatic intraepithelial neoplasia and high-grade dysplasia. Prostatic glands exhibiting reactive dysplasia had a stronger staining for oxidative DNA damage, increased epithelial cell proliferation, and a decrease in androgen receptor, GSTP1, p27Kip1, and PTEN expression, when compared with control prostate glands. These data demonstrate that chronic inflammation induces focal prostatic glandular atypia and suggest a potential linkage between inflammation and prostatic neoplasia.
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影响因子：
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作者：
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