Joo Moon Kyung, Park Jong-Jae, Yoo Hyo Soon, Lee Beom Jae, Chun Hoon Jai, Lee Sang Woo, Bak Young-Tae
Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine Guro Hospital, Seoul, Korea.
Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine Anam Hospital, Seoul, Korea.
J Gastroenterol Hepatol. 2016 Oct;31(10):1717-1726. doi: 10.1111/jgh.13330.
The aim of this study was to compare HOXB7 expression level between gastric cancer and non-cancerous gastric tissues. Additionally, the functional effects of HOXB7, including its pro-migration or invasion and anti-apoptosis roles, were evaluated in gastric cancer cells.
Both gene and protein expression levels of HOXB7 were examined in gastric cancer cell lines, and HOXB7 expression was compared between primary or metastatic gastric cancer tissues and chronic gastritis or intestinal metaplasia tissues. Functional studies included a wound healing assay, a Matrigel invasion assay, and an Annexin-V assay were performed, and Akt/PTEN activity was measured by western blotting.
Both gene and protein expression levels of HOXB7 could be clearly detected in various gastric cancer cell lines except MKN-28 cell. HOXB7 expression was significantly higher in primary or metastatic gastric cancer tissues than in chronic gastritis or intestinal metaplasia tissues. HOXB7 knockdown led to inhibition of cell invasion and migration, had an apoptotic effect, downregulated phosphor-Akt, and upregulated PTEN in AGS and SNU-638 cells. Reinforced expression of HOXB7 caused the opposite effects in MKN-28 and MKN-45 cells.
Our study suggests that HOXB7 has an oncogenic role in gastric cancer, which might be related to the modulation of Akt/PTEN activity to induce cell migration/invasion and anti-apoptotic effects.
本研究旨在比较胃癌组织与非癌性胃组织中HOXB7的表达水平。此外，还评估了HOXB7在胃癌细胞中的功能作用，包括其促迁移或侵袭以及抗凋亡作用。
检测了胃癌细胞系中HOXB7的基因和蛋白表达水平，并比较了原发性或转移性胃癌组织与慢性胃炎或肠化生组织中HOXB7的表达。功能研究包括进行伤口愈合试验、基质胶侵袭试验和膜联蛋白-V试验，并通过蛋白质印迹法检测Akt/PTEN活性。
除MKN-28细胞外，在各种胃癌细胞系中均能清楚检测到HOXB7的基因和蛋白表达水平。原发性或转移性胃癌组织中HOXB7的表达明显高于慢性胃炎或肠化生组织。在AGS和SNU-638细胞中，敲低HOXB7导致细胞侵袭和迁移受到抑制，具有凋亡作用，下调磷酸化Akt水平，并上调PTEN水平。增强HOXB7的表达在MKN-28和MKN-45细胞中产生相反的作用。
我们的研究表明，HOXB7在胃癌中具有致癌作用，这可能与调节Akt/PTEN活性以诱导细胞迁移/侵袭和抗凋亡作用有关。
