目的：观察PcG 家族蛋白Bmi-1在食管上皮组织中的表达情况，探讨Bmi-1在食管上皮组织发育过程中的表达规律及意义。方法：采用免疫组化法检测120例小鼠胚胎、20例成年小鼠、15例人体胚胎、18例正常成年人食管上皮组织及17例食管癌组织中Bmi-1的表达，并利用图像分析软件对Bmi-1的表达强度进行定量分析，运用统计软件对各组数据进行统计学分析。结果： Bmi-1在各组食管上皮组织及食管癌组织中均存在表达，但各组表达强度不同，差异有统计学意义(P＜0.05)。 Bmi-1在小鼠与人体胚胎时期食管上皮组织中的表达量均高于生后食管上皮组织。 Bmi-1在人体胚胎、正常成年人食管上皮及食管癌组织中表达强度不同，差异有统计学意义(P＜0.01)，并且在食管癌组织中呈强阳性表达。结论：Bmi-1在不同发育阶段食管上皮组织的表达强度不同，与食管上皮组织的发育密切相关。另外，检测Bmi-1的表达对研究食管上皮组织的发育生物学与食管癌的发生发展具有一定意义。
Abstract
Objective To observe the Bmi-1 protein expression in esophageal epithelial tissues ,and to explore the relationship between the expression pattern of Bmi-1 and the development of esophageal epithelial tissues. Methods Immunohistochemistry was used to measure the expression of Bmi-1 in esophageal epithelial tissues of 120 cases mouse in different development time,15 cases human embryos, 18 cases normal adult human and 17 cases human esophageal squamous cell carcinoma (ESCC), then the level of Bmi-1 protein expression in these samples were analyzed by image analysis software, and the statistical analyses were applied to test the relationship between the expression of Bmi-1 and each group. Results Bmi-1 was found to expression in every time of development, but the differences were present in the protein expression level (P＜0.05). Expression of Bmi-1 protein was higher at embryo stage than that after birth both in mice and human. Compared with esophageal tissue of normal adult human, Bmi-1 overexpressed both in human esophageal squamous cell carcinoma and human embryo(P＜0.01). Conclusions The expression of Bmi-1 closely was related with the development of esophageal epithelium.Furthermore,there were a potential significance to detection of the Bmi-1 expression for the research in the developmental biology of esophageal epithelium and the cytobiology of esophageal cancer.
关键词
Bmi-1 /
食管上皮组织 /
发育 /
免疫组织化学
Key words
Bmi-1 /
esophageal epithelium /
development /
Immunohistochemistry
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1]Haupt Y, Alexander W S, Barri G, et al.Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice [J]. Cell, 1991, 65(5):753-763.
[2]Park IK,Qian D,Kiel M, et al . Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells [J].Nature 2003, 423:302-305.
[3]Leung C,Lingbeek M,Shakhova O,et al.Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas [J].Nature 2003,428:337-341.
[4]郑翔宇,朱杰,王艺芳等. Bmi-1-siRNA对肺腺癌A549细胞体内外增殖能力的影响[J]. 中国癌症杂志,2013,07:505-511.
[5]Yoshikawa R, Tsujimura T, Tao L, et al. Theoncoprotein and stem cell renewal factor BMI1 associates with poorclinical outcome in oesophageal cancer patients undergoing preoper-ative chemoradiotherapy [J].BMC Cancer 2012;12:461.
[6]Alkema MJ,Wiegant J,Raap AK,et al. Charaeterization and ehromosomal loealizationof the human Proto-oneogene Bmi-1[J].Hum Mol Genet 1993,2(10):1597-1603.
[7]Park IK,Qian D,Kiel M, et al . Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells [J].Nature 2003, 423:302-305.
[8]Lessard J, Sauvageau G et al. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cell [J].Nature 2003, 423:255-260.
[9]Molofsky AV, Pardal R, Iwashita T, et al. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation [J].Nature, 2003, 425: 962-967.
[10] Chatoo W, Abdouh M, Duparc RH, et al. Bmil distinguishes immature retinal progenitor/stem cells from the main progenitor cell population and is required for normal retinal development [J].Stem Cells 2010, 28:1412-1423.
[11]Cordisco S, Maurelli R, Bondanza S, Stefanini M, et al. Bmi-1 reduction plays a key role in physiological and premature aging of primary human keratinocytes [J].J Invest Dermatol. 2010, 130(4):1048-62.
[12]Sangiorgi E, Capecchi MR,et al. Bmi-l is expressed in vivo in intestinal stem cells [J].Nature Genetics 2008, 40:915-920.
[13]Siddique, H.R. M. Saleem, et al. Role of Bmi-1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences [J].Stem Cells, 2012, 30(3):372-378.
[14] Bonnie C,?Santhoshi B,?XiaYL,et al. Clinicopathologic characteristics of high expression of Bmi-1 in esophageal adenocarcinoma and squamous cell carcinoma [J].BMC Gastroenterology ,2012 ,12:146.
[15] He XT,Cao XF,Ji L,et a1.Association between Bmi-l and clinicopathological status of esophageal squamous cell carcinoma [J].World J Gastroenterol,2009,15(19):2389-2394.
[16] Lv J , Cao XF ,Ji L, Zhu B et a1.Association of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 with the prognosis of esophageal squamous cell carcinoma [J].Med Oncol 2012, 29:151–160.
[17].Kim T. H，Lee H. M.Lee S. H，et al.Expression and distribution patterns of the stem cell marker, nestin, and the stem cell renewal factor, BMI-1, in normal human nasal mucosa and nasal polyps [J].Acta Oto-laryngologica, 2009. 129(9): 996-1001.
[18]Pan Q, A.M. Nicholson, Barr H, et al.Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus[J]. Gastroenterology 144 (4): 761-770.
[19] He S,Iwashita T,Buchstaller J,et al. Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and neurogenesis in culture but has little effect on these functions in vivo [J]. Developmental Biology, 2009. 328(2):257-272.
[20]张世庆. 精原干细胞自增殖分子机制研究[D].中国人民解放军军事医学科学院,2007.
[21]阮艳. 过表达癌基因Bmi-1促进鼠源胚胎干细胞自我更新[D].第三军医大学,2009.
[22]Hwang CC, Nieh S, Lai CH,et al.A retrospective review of the prognostic value of ALDH- 1, Bmi-1 and Nanog stem cell markers in esophageal squamous cell carcinoma [J ].PLoS ONE 2014 9(8): e105676.
基金
中国国家自然科学基金;新疆生产建设兵团科技支疆计划;石河子大学国家级大学生创新创业训练计划
