Li Yanke, Sun Zhe, Zhu Zhi, Zhang Junyan, Sun Xu, Xu Huimian
Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City, 110001, People's Republic of China.
Tumour Biol. 2014 May;35(5):4363-8. doi: 10.1007/s13277-013-1573-6. Epub 2013 Dec 29.
The pre-leukemia transcription factor 3 (PBX3) is a member of the PBX family of transcription factors, which is known to increase DNA-binding/transcriptional activity of HOX proteins and regulate genes involved in development. Recently, PBX3 was reported to be involved in a variety of cancers, while its implication in gastric cancer is unclear. This study aimed to investigate its clinical significance and biological function in gastric cancer. PBX3 expression was analyzed in 90 gastric cancer specimens using immunohistochemistry. PBX3 was overexpressed in 30 cases (33.33%). Importantly, PBX3 overexpression positively correlated with advanced invasion depth (p = 0.0017), Clinical stage (p = 0.0127) and grade of tumor differentiation (p = 0.0158). PBX3 was also overexpressed in gastric cancer cell lines. Plasmid transfection was performed in AGS and SGC-7901 gastric cancer cell line with low endogenous PBX3 expression. MTT and colony formation assay were carried out to assess the role of PBX3 in proliferation. PBX3 overexpression in gastric cancer cell lines accelerated cell proliferation rate and colony formation ability, with upregulation of PCNA expression. In addition, matrigel invasion assay showed that PBX3 transfection also increased cell-invading ability. These results validate the role of PBX3 as a clinically relevant oncoprotein and establish PBX3 as a promising therapeutic target of gastric cancer.
白血病前期转录因子3（PBX3）是转录因子PBX家族的成员之一，已知其可增强HOX蛋白的DNA结合/转录活性，并调控参与发育的基因。最近，有报道称PBX3与多种癌症有关，但其在胃癌中的作用尚不清楚。本研究旨在探讨其在胃癌中的临床意义和生物学功能。采用免疫组织化学方法分析了90例胃癌标本中PBX3的表达情况。30例（33.33%）标本中PBX3呈过表达。重要的是，PBX3过表达与侵袭深度增加（p = 0.0017）、临床分期（p = 0.0127）和肿瘤分化程度（p = 0.0158）呈正相关。PBX3在胃癌细胞系中也呈过表达。对内源性PBX3表达较低的AGS和SGC-7901胃癌细胞系进行质粒转染。采用MTT和集落形成试验评估PBX3在增殖中的作用。胃癌细胞系中PBX3过表达加速了细胞增殖率和集落形成能力，同时PCNA表达上调。此外，基质胶侵袭试验表明，PBX3转染也增加了细胞侵袭能力。这些结果证实了PBX3作为一种临床相关癌蛋白的作用，并确立了PBX3作为胃癌有前景的治疗靶点。
