Department of Thoracic Surgery, The Second Affiliated Hospital of Dalian Medical University, Zhongshan Road 467, Dalian, Liaoning 116023, China.
Cancer Cell Int. 2014 Jan 31;14(1):12. doi: 10.1186/1475-2867-14-12.
Esophageal squamous incidence in many developed countries has increased dramatically over last decades, while the underlying mechanism of the biogenesis of ES was still unknown.
Here, we investigate 1001 subjects with esophageal cancer recruited from the affiliated hospital of Shanghai Jiao Tong University from Jan. 1, 2001 to Feb. 2, 2004. Single nucleotide polymorphism (SNP) of alcohol dehydrogenase-1B (ADH1B) was performed, and the recombinant plasimd containing ADH1B was constructed. Then, the ADH1B was purified and the enzymatic activity was assayed according to the methodology of Quayle. Furthermore, the effect of ADH1B on proliferation of human esophageal squamous cell lines was determined and the underlying mechanism of ADH1B was investigated.
Logistic regression analyses revealed that subjects carrying the GG variant homozygote had a significant 2.81-fold (adjusted OR = 2.81; 95% CI = 2.18-3.62) increased risk of esophageal cancer. We found that SNP of ADH1B (GG) significantly promotes cell proliferation in ESGG. ADH1B (GG) could down-regulate endogenous ADH1B expression at posttranscriptional level. Moreover, re-expression of ADH1B in cells transfected with ADH1B (AA) significantly inhibits cell proliferation.
Our data implied that ADH1B (GG) could promote cell proliferation in human ESGG through regulating the enzyme activity of ADH1B. Therefore, we propose that ADH1B might be used as a therapeutic agent for human ESGG.
在过去几十年中，许多发达国家的食管鳞癌发病率显著增加，而 ES 发生的潜在机制尚不清楚。
本研究调查了 2001 年 1 月 1 日至 2004 年 2 月 2 日期间从上海交通大学附属医院招募的 1001 名食管癌患者。对其进行了醇脱氢酶-1B（ADH1B）单核苷酸多态性（SNP）检测，并构建了含有 ADH1B 的重组质粒。然后，根据 Quayle 的方法对 ADH1B 进行纯化和酶活性测定。进一步测定 ADH1B 对人食管鳞癌细胞系增殖的影响，并探讨 ADH1B 的潜在作用机制。
logistic 回归分析显示，携带 GG 纯合变异体的个体患食管癌的风险显著增加 2.81 倍（调整 OR = 2.81；95%CI = 2.18-3.62）。我们发现 ADH1B 的 SNP（GG）显著促进 ESGG 中的细胞增殖。ADH1B（GG）可在转录后水平下调内源性 ADH1B 的表达。此外，在转染 ADH1B（AA）的细胞中重新表达 ADH1B 可显著抑制细胞增殖。
我们的数据表明，ADH1B（GG）可通过调节 ADH1B 的酶活性促进人 ESGG 中的细胞增殖。因此，我们提出 ADH1B 可作为治疗人 ESGG 的候选药物。
