PTEN 缺失诱导人结肠癌细胞发生上皮-间质转化。
PTEN loss induces epithelial--mesenchymal transition in human colon cancer cells.
机构信息
Markey Cancer Center, University of Kentucky, Lexington, KY 40536-0093, USA.
出版信息
Anticancer Res. 2009 Nov;29(11):4439-49.
Abstract
BACKGROUND
The epithelial-mesenchymal transition is a critical early event in the invasion and metastasis of many types of cancer, including colorectal cancer (CRC). Chronic inflammation is an inducer of several cancer types and inflammatory cytokines have been implicated in tumor invasion.
MATERIALS AND METHODS
Human colon cancer cell lines HCT116 and SW480 were transfected with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) siRNA or non-targeting control (NTC). Invasiveness was measured using a modified Boyden chamber assay and migration was assessed using a scratch assay.
RESULTS
PTEN knockdown increased the invasion and migration of CRC cells and the addition of medium containing tumor necrosis factor-alpha (TNF-alpha) further enhanced the migration and invasion. PTEN knockdown resulted in nuclear beta-catenin accumulation and increased expression of downstream proteins c-Myc and cyclin D1.
CONCLUSION
Our study supports the findings of clinical studies identifying an association of PTEN loss with late stage cancer. Cellular factors secreted from the surrounding tumor milieu likely act in concert with genetic changes in the tumor cells and contribute to enhanced tumor invasion.
摘要
背景
上皮-间充质转化是许多类型癌症（包括结直肠癌）侵袭和转移的关键早期事件。慢性炎症是多种癌症的诱因，炎症细胞因子已被牵涉到肿瘤侵袭中。
材料和方法
用人结肠癌细胞系 HCT116 和 SW480 转染磷酸酶和张力蛋白同源物缺失于染色体 10（PTEN）siRNA 或非靶向对照（NTC）。使用改良的 Boyden 室测定法测量侵袭性，使用划痕测定法评估迁移。
结果
PTEN 敲低增加了结直肠癌细胞的侵袭和迁移，并且添加含有肿瘤坏死因子-α（TNF-α）的培养基进一步增强了迁移和侵袭。PTEN 敲低导致核β-catenin 积累和下游蛋白 c-Myc 和 cyclin D1 的表达增加。
结论
我们的研究支持临床研究的发现，即 PTEN 缺失与晚期癌症有关。来自周围肿瘤微环境的细胞因子可能与肿瘤细胞中的遗传变化协同作用，导致肿瘤侵袭增强。
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