Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
Neoplasma. 2012;59(4):416-23. doi: 10.4149/neo_2012_054.
The oncogenic isoform of the p63 protein, ΔNp63α, has been found to be overexpressed in numerous human squamous cell carcinomas. However, the role of ΔNp63α in human gastric cancer remains unknown. To evaluate this role, we screened a panel of gastric cancer cell lines for ΔNp63α expression and found that they are correlated with the differentiation status of the cell lines. Using the MKN28 gastric cancer cell line for loss-of-function or gain-of-function of ΔNp63α in our experiments, we observed that forced expression of ΔNp63α promoted cell proliferation as assessed by the MTT and colony formation assays, and increased the GATA-6 expression. In contrast, down-regulation of ΔNp63α via small interfering RNA suppressed cell proliferation, induced cell apoptosis, and reduced the expression of GATA-6. In conclusion, our data suggest that ΔNp63α plays an important role in cell growth and proliferation of gastric cancer cells, which may be associated with the regulation of GATA-6 expression. This is the first study exploring the biological functions and the underlying mechanism of ΔNp63α during gastric cancer development. It also identifies potential targets for anti-tumor treatment.
p63 蛋白的致癌异构体 ΔNp63α 在许多人类鳞状细胞癌中被发现过度表达。然而，ΔNp63α 在人类胃癌中的作用仍不清楚。为了评估其作用，我们筛选了一组胃癌细胞系以检测 ΔNp63α 的表达情况，发现其与细胞系的分化状态相关。在我们的实验中，使用 MKN28 胃癌细胞系对 ΔNp63α 进行功能丧失或功能获得，我们观察到强制表达 ΔNp63α 通过 MTT 和集落形成测定促进细胞增殖，并增加 GATA-6 的表达。相比之下，通过小干扰 RNA 下调 ΔNp63α 可抑制细胞增殖，诱导细胞凋亡，并降低 GATA-6 的表达。总之，我们的数据表明 ΔNp63α 在胃癌细胞的生长和增殖中发挥重要作用，这可能与 GATA-6 表达的调节有关。这是首次研究探索 ΔNp63α 在胃癌发展过程中的生物学功能和潜在机制。它还确定了抗肿瘤治疗的潜在靶点。
