Gou Wen-feng, Sun Hong-zhi, Zhao Shuang, Niu Zhe-feng, Mao Xiao-Yun, Takano Yasuo, Zheng Hua-chuan
Cancer Research Center, The First Affiliated Hospital of Liaoning Medical University, JinZhou, PR China, .
Indian J Med Res. 2014 Apr;139(4):561-7.
BACKGROUND & OBJECTIVES: ING3 (inhibitor of growth protein 3) overexpression decreased S-phase cell population and colony-forming efficiency, and induced apoptosis at a p53-mediated manner. The aim of this study was to investigate the clinicopathological and prognostic significance of ING3 expression in colorectal carcinogenesis and subsequent progression.
ING3 expression was examined by immunohistochemistry on tissue microarray containing colorectal non-neoplastic mucosa (NNM), adenoma and adenocarcinoma. Colorectal carcinoma tissue and cell lines were studied for ING3 expression by Western blot or RT-PCR.
ING3 mRNA was differentially expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620 and WiDr cells. Carcinomas showed significantly lower ING3 expression than matched NNM at mRNA level (P< 0.05), but not at protein level. Immunohistochemically, ING3 expression was significantly decreased from NNM, adenoma to adenocarcinoma (P< 0.05). ING3 expression was not correlated with age, sex, tumour size, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumour- node- metastasis staging or differentiation. Kaplan-Meier analysis indicated that ING3 protein expression was not associated the prognosis of the patients with colorectal carcinoma (P< 0.05).
INTERPRETATION & CONCLUSIONS: Our study showed that downregulated ING3 expression might play an important role in colorectal adenoma-adenocarcinoma sequence. Further studies are required to understand the mechanism.
生长抑制蛋白3(ING3)过表达可减少S期细胞群体并降低集落形成效率,且以p53介导的方式诱导细胞凋亡。本研究旨在探讨ING3表达在结直肠癌发生及后续进展中的临床病理及预后意义。
采用免疫组织化学方法检测包含结直肠非肿瘤性黏膜(NNM)、腺瘤和腺癌的组织芯片中ING3的表达。通过蛋白质印迹法或逆转录-聚合酶链反应(RT-PCR)研究结直肠癌组织及细胞系中ING3的表达情况。
ING3 mRNA在Colo201、Colo205、DLD-1、HCT-15、HCT-116、HT-29、KM-12、SW480、SW620和WiDr细胞中差异表达。在mRNA水平,癌组织中ING3的表达明显低于配对的NNM(P<0.05),但在蛋白质水平未见明显差异。免疫组织化学结果显示,从NNM、腺瘤到腺癌,ING3的表达显著降低(P<0.05)。ING3的表达与年龄、性别、肿瘤大小、浸润深度、淋巴管或静脉侵犯、淋巴结转移、肿瘤-淋巴结-转移分期或分化无关。Kaplan-Meier分析表明,ING3蛋白表达与结直肠癌患者的预后无关(P<0.05)。
我们的研究表明,ING3表达下调可能在结直肠腺瘤-腺癌序列中起重要作用。需要进一步研究以了解其机制。