Department of Pathophysiology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Dig Dis Sci. 2012 Jul;57(7):1838-46. doi: 10.1007/s10620-012-2108-5. Epub 2012 Mar 27.
HAX-1 is an anti-apoptotic factor and regulates the expression of DNA pol β. Interestingly, DNA polymerase pol β is overexpressed in esophageal squamous cell carcinoma (ESCC). However, the functional role of HAX-1 in ESCC remains unclear.
To investigate the role of HAX-1 in chemoresistance, invasion, and tumorigenicity of ESCC.
Lentivirus-mediated overexpression or knockdown of HAX-1 was employed to establish ESCC EC9706 cell lines that expressed HAX-1 at different levels. The biological behaviors of these engineered cells were characterized in vitro and in vivo using a xenograft nude mice model. In addition, HAX-1 and pol β expression in the tumor tissues was detected by RT-PCR and immunohistochemistry.
HAX-1 overexpression promoted cell proliferation and resistance against cisplatin, increased cell invasion and suppressed apoptosis along with increased pol β expression. Conversely, HAX-1 knockdown inhibited the malignant phenotypes of EC9706 cells. The xenograft nude mice model demonstrated that HAX-1 overexpression or depletion led to increased or decreased tumor growth in vivo, respectively. Furthermore, a positive correlation of HAX-1 and pol β expression in the tumor tissues was observed.
HAX-1 promotes the proliferation, chemoresistance, invasion, and tumorigenicity of ESCC, and this is correlated with increased poly β expression. HAX-1 may represent a potential target to overcome the resistance and metastasis of ESCC.
HAX-1 是一种抗凋亡因子，可调节 DNA 聚合酶 pol β 的表达。有趣的是，DNA 聚合酶 pol β 在食管鳞状细胞癌（ESCC）中过表达。然而，HAX-1 在 ESCC 中的功能作用尚不清楚。
研究 HAX-1 在 ESCC 化疗耐药、侵袭和致瘤性中的作用。
采用慢病毒介导的过表达或敲低 HAX-1，建立 HAX-1 表达水平不同的 ESCC EC9706 细胞系。利用裸鼠异种移植模型，在体外和体内对这些工程细胞的生物学行为进行了特征描述。此外，通过 RT-PCR 和免疫组织化学检测肿瘤组织中 HAX-1 和 pol β 的表达。
HAX-1 过表达促进细胞增殖和对顺铂的耐药性，增加细胞侵袭并抑制凋亡，同时增加 pol β 的表达。相反，HAX-1 敲低抑制了 EC9706 细胞的恶性表型。裸鼠异种移植模型表明，HAX-1 过表达或耗竭分别导致体内肿瘤生长增加或减少。此外，还观察到肿瘤组织中 HAX-1 和 pol β 表达呈正相关。
HAX-1 促进 ESCC 的增殖、化疗耐药性、侵袭和致瘤性，这与 pol β 表达增加有关。HAX-1 可能成为克服 ESCC 耐药性和转移的潜在靶点。
