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生长抑制蛋白2在正常组织和癌组织中的表达谱:一项免疫组织化学筛查分析。

Expression profiles of inhibitor of growth protein 2 in normal and cancer tissues: An immunohistochemical screening analysis.

作者信息

Zhao Shuang, Yang Xue-Feng, Gou Wen-Feng, Lu Hang, Li Hua, Zhu Zhi-Tu, Sun Hong-Zhi, Zheng Hua-Chuan

机构信息

Cancer Center and Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.

出版信息

Mol Med Rep. 2016 Feb;13(2):1881-7. doi: 10.3892/mmr.2015.4723. Epub 2015 Dec 28.

DOI:10.3892/mmr.2015.4723
PMID:26717876
Abstract

Inhibitor of growth protein 2 (ING2) has an important role in the regulation of chromatin remodeling, cell proliferation, cell‑cycle arrest, senescence and apoptosis. The present study performed an immunohistochemical analysis for expression profiling of ING2 protein in an array of tissues comprising normal mouse and human tissues, as well as human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung (n=192) carcinoma tissues. In mouse tissues, ING2 was detected in the nuclei and cytoplasm of the glandular epithelium of breast, hepatocytes, intestine, bronchium and alveoli, as well as the squamous epithelium of skin and glomeruli, and in myocardial cells, while it was located in the cytoplasm of renal tubules and striated muscle cells. ING2 protein was scattered in the brain and spleen. In human tissues, ING2 protein was principally distributed in the cytoplasm, while in it was present in the cytoplasm and nuclei in the stomach, intestine, cervix, endometrium trachea, breast and pancreas. The nuclear location of ING2 in the stomach was more prominent than that in the cytoplasm. High ING2 immunoreactivity was detected in the tongue, stomach, skin, pancreas, cervix and breast, whereas weakly in the brain stem, thymus, thyroid, lung, striated muscle, testis, bladder and ovary. In total, 617 out of 1,194 of the tested cancer tissues (51.7%) were ING2-positive. In most cases, ING2 expression was found to be restricted to the cytoplasm of all cancer tissues, while in certain cancer types, including renal clear cell, ovarian and colorectal carcinoma, it was occasionally present in the nuclei. Among the cancer tissues examined, ING2 was most frequently expressed in breast cancer (67.4%) and gynecological cancer types, including ovarian cancer (61.5%) and endometrial cancer (57.3%). Compared with that in the respective normal tissues, ING2 expression in breast cancer tissues was decreased, while that in cervical cancer was upregulated in the nuclei as well as the cytoplasm. In endometrial cancer, expression of ING2 was increased in the nuclei and declined in the cytoplasm compared with that in the normal endometrium. ING2‑positive cases were less frequent for renal clear cell carcinoma (17.7%). The results of the present study suggested that ING2 may be involved in the repair and regeneration of organs or tissues and is associated with breast and gynecological carcinogenesis.

摘要

生长抑制蛋白2(ING2)在染色质重塑、细胞增殖、细胞周期阻滞、衰老和凋亡的调节中发挥重要作用。本研究采用免疫组织化学分析法,对包括正常小鼠和人类组织,以及人类肝细胞癌(n = 62)、肾透明细胞癌(n = 62)、胰腺癌(n = 62)、食管鳞状细胞癌(n = 45)、宫颈鳞状细胞癌(n = 31)、乳腺癌(n = 144)、胃癌(n = 196)、结直肠癌(n = 96)、卵巢癌(n = 208)、子宫内膜癌(n = 96)和肺癌(n = 192)组织在内的一系列组织中的ING2蛋白表达谱进行分析。在小鼠组织中,ING2在乳腺腺上皮、肝细胞、肠、支气管和肺泡的细胞核及细胞质中,以及皮肤和肾小球的鳞状上皮细胞、心肌细胞中均有检测到,而在肾小管和横纹肌细胞的细胞质中也有分布。ING2蛋白在脑和脾中呈散在分布。在人类组织中,ING2蛋白主要分布在细胞质中,而在胃、肠、宫颈、子宫内膜、气管、乳腺和胰腺中,ING2蛋白同时存在于细胞质和细胞核中。ING2在胃中的核定位比细胞质中更为明显。在舌、胃、皮肤、胰腺、宫颈和乳腺中检测到较高的ING2免疫反应性,而在脑干、胸腺、甲状腺、肺、横纹肌、睾丸、膀胱和卵巢中则较弱。在1194个检测的癌组织中,共有617个(51.7%)为ING2阳性。在大多数情况下,ING2表达局限于所有癌组织的细胞质中,而在某些癌类型中,包括肾透明细胞癌、卵巢癌和结直肠癌,ING2偶尔也存在于细胞核中。在所检查的癌组织中,ING2在乳腺癌(67.4%)和妇科癌类型中最常表达,包括卵巢癌(61.5%)和子宫内膜癌(57.3%)。与各自的正常组织相比,乳腺癌组织中ING2表达降低,而宫颈癌中ING2在细胞核和细胞质中的表达均上调。在子宫内膜癌中,与正常子宫内膜相比,ING2在细胞核中的表达增加,在细胞质中的表达下降。肾透明细胞癌中ING2阳性病例较少(17.7%)。本研究结果表明,ING2可能参与器官或组织的修复和再生,并与乳腺癌和妇科肿瘤发生相关。

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