HSP70、P53及β-Catenin在肠道息肉恶变中的表达及相关性-现代医学

HSP70、P53及β-Catenin在肠道息肉恶变中的表达及相关性

单位：1. 沈阳二四二医院急诊科, 辽宁沈阳 110034;
2. 沈阳二四二医院病理科, 辽宁沈阳 110034;
3. 沈阳二四二医院普通外科, 辽宁沈阳 110034

分类号：R735.3

出版年·卷·期（页码）：2020·48·第一期（39-44）

摘要：

目的： 研究热休克蛋白70（Heat shock protein 70，HSP70）、P53及β-Catenin在家族性腺瘤性息肉病（familial adenomatous polyposis，FAP）肠道息肉恶变中的表达及相关性。方法： 采集6周龄及9周龄APC^Δ716/+小鼠的肠道标本，通过免疫组织化学染色、蛋白质免疫印迹分析及RT-PCR等实验方法明确良性息肉及息肉恶变组织中HSP70、P53及β-Catenin的表达及相关性。方法： 肠道息肉恶变组织中HSP70及P53免疫组织化学染色的平均光密度较6周小鼠良性息肉显著增加（P均 < 0.001），HSP70及P53的蛋白质免疫印迹分析条带较良性息肉明显增加，HSP70及P53的mRNA表达也较良性息肉显著增强（P均 < 0.001）；但息肉恶变组织β-Catenin的平均光密度及mRNA与良性息肉比较虽然略有升高，但未见显著差异（P=0.076，P=0.091）。HSP70 和P53 在息肉恶变组织中的表达存在明显的正相关（r=0.731，P=0.007），但HSP70与β-Catenin的表达未见明显相关性。方法： FAP肠道息肉恶变组织中HSP70及P53表达均较良性息肉显著升高，其表达具有呈明显的正相关，提示HSP70可能通过与P53相互作用，促进FAP的肠道息肉恶变。该发现为HSP70应用于抑制FAP肠道息肉恶变提供重要的理论依据。

Objective: To investigate the expression and correlation of Heat shock protein 70(HSP70), P53 and β-Catenin in malignant polyps in familial adenomatous polyposis (FAP). Methods: The intestinal specimens of APC^Δ716/+mice were collected at 6 weeks and 9 weeks. Immunohistochemical staining, western blot and RT-PCR were performed to determine the expression and correlation of HSP70, P53 and β-Catenin in malignant polyps. Results: The average light densities of HSP70 and P53 in malignant polyps were significantly higher than those of benign polyps (P all<0.001) in immunohistochemical staining, and the strips of HSP70 and P53 in malignant polyps were significantly stronger than those in benign polyps in western blot analysis. The mRNA expressions of HSP70 and P53 in malignant polyps were significantly higher than those of benign polyps (P all<0.001). However, although the average light density and mRNA of β-Catenin in malignant polyps increased slightly, there were no significant difference compared with benign polyps (P=0.076, P=0.091). The expressions of HSP70 and P53 protein showed a positive correlation (r=0.731,P=0.007) in malignant polyps, while there was no obvious correlation between the expressions of HSP70 and β-Catenin. Conclusion: The expressions of HSP70 and P53 in malignant polyps of FAP are significantly higher than those in benign polyps, and there is a positive correlation between the expressions of HSP70 and P53 proteins in malignant polyps. HSP70 may promote the carcinogenesis of benign polyps in FAP through the interaction with P53. These findings provide an important theoretical basis for the application of HSP70 in FAP preventing intestinal polyps from occurring

参考文献：

[1] LIU Q,LI X,LI S,et al.Three novel mutations of APC gene in Chinese patients with familial adenomatous polyposis[J].Tumour Biol,2016,37(8):11421-11427.
[2] CHINTALACHERUVU L M,SHAW T,BUDDAM A,et al.Major hereditary gastrointestinal cancer syndromes:a narrative review[J].J Gastrointestin Liver Dis,2017,26(2):157-163.
[3] KOBAYASHI H,ISHIDA H,UENO H,et al.Association between the age and the development of colorectal cancer in patients with familial adenomatous polyposis:a multi-institutional study[J].Surg Today,2017,47(4):470-475.
[4] SEPTER S,LAWSON C E,ANANT S,et al.Familial adenomatous polyposis in pediatrics:natural history,emerging surveillance and management protocols,chemopreventive strategies,and areas of ongoing debate[J].Fam Cancer,2016,15(3):477-485.
[5] MAEHATA Y,EAAKI M,HIRAHASHI M,et al.Duodenal adenomatosis in Japanese patients with familial adenomatous polyposis[J].Dig Endosc,2014,26 S (2):30-34.
[6] OSHIMA H,KOK S Y,NAKAYAMA M,et al.Stat3 is indispensable for damage-induced crypt regeneration but not for Wnt-driven intestinal tumorigenesis[J].FASEB Journal,2019,33(2):1873-1886.
[7] NAKANISHI T,OHNO Y,AOTANI R,et al.A novel role for OATP2A1/SLCO2A1 in a murine model of colon cancer[J].Sci Rep,2017,7(1):16567.
[8] 沈晓东.Id2在小鼠家族性腺瘤性息肉病发生中的作用[J].肿瘤防治研究,2013,40(10):930-934.
[9] MYMRIKOV E V,DAAKE M,RICHTER B,et al.The chaperone activity and substrate spectrum of human small heat shock proteins[J].J Biol Chem,2017,292(2):672-684.
[10] BOUDESCO C,CAUSE S,JEGO G,et al.HSP70:a cancer target inside and outside the cell[J].Methods Mol Biol,2018,1709:371-1396.
[11] SVERCHINSKY D V,NIKOTINA A D,KOMAROVA E Y,et al.Etoposide-induced apoptosis in cancer cells can be reinforced by an uncoupled link between HSP70 and Caspase-3[J].Int J Mol Sci,2018,19(9):2519.
[12] 缑文斌,田素升,李长风.P53和HSP70在肝癌、肝硬化及肝血管瘤的表达及意义[J].肝脏,2018,23(5):410-413.
[13] LI X L,ZHAO X L,DONG Q,et al.Enhancement of immunogenicity of murine lymphocytic leukemia cells by transfection with BCG Heat Shock Protein 70 gene[J].Int Immunopharmacol,2013,15(1):1-5.
[14] BAYER C,LIEBHARDT M,SCHMID T,et al.Validation of Heat Shock Protein 70 as a tumor-specific biomarker for monitoring the outcome of radiation therapy in tumor mouse models[J].Int J Radiat Oncol Biol Phys,2014,88(3):694-700.
[15] 沈晓东,傅庆国,孟凡东,等.手术联合热休克蛋白70对荷瘤小鼠的治疗作用[J].肿瘤防治杂志,2003,10(5):487-489.
[16] 肖海,叶晓星,徐仙赟,等.Col-Ⅳ、LN、FN和MMP-9在不同时期婴幼儿型血管瘤中的表达和意义[J].中华小儿外科杂志,2017,38(1):4-9.
[17] 王丹,杨晶,张昭,等.家族性腺瘤性息肉病最新研究进展[J].中国肛肠病杂志,2018,38(9):62-65.
[18] DELKER D A,WOOD A C,SNOW A K,et al.Chemoprevention with cyclooxygenase and epidermal growth factor receptor inhibitors in familial adenomatous polyposis patients:mRNA signatures of duodenal neoplasia[J].Cancer Prev Res,2018,11(1):4-15.
[19] MOSES M A,KIM Y S,RIVERA-MARQUEZ G M,et al.Targeting the HSP40/HSP70 chaperone axis as a novel strategy to treat castration-resistant prostate cancer[J].Cancer Res,2018,78(14):4022-4035.
[20] 黄自明,孙圣荣.热休克蛋白70在乳腺癌中的表达及其对体外乳腺癌细胞株生物学功能的影响[J].中华实验外科杂志,2015,32(10):2440-2443.
[21] 徐道晶,张晓,孙荣同.HSP90和HSP70与肿瘤发生的研究进展[J].医学检验与临床,2016,27(9):52-54,67.
[22] SÖDERSTRÖM H K,KAUPPI J T,OKSALA N,et al.Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma[J].World J Clin Cases,2019,7(3):260-269.
[23] RIVLIN N,BROSH R,OREN M.et a1.Mutations in tile P53 tumorsuppressor gene:important milestones at the various steps of tumorigenesis[J].Genes Cancer,2011,2(4):466-474.
[24] SIKORSKA A,FLISIKOWSKA T,STACHOWIAK M,et al.Elevated expression of P53 in early colon polyps in a pig model of human familial adenomatous polyposis[J].J Appl Genet,2018,59(4):485-491.
[25] RASHID M,FISCHER A,WILSON C H,et al.Adenoma development in familial adenomatous polyposis and MUTYH-associated polyposis:somatic landscape and driver genes[J].J Pathol,2016,238(1):98-108.
[26] WANG Z,GOU W B,LIU M,et al.Expression of P53 and HSP70 in chronic hepatitis,liver cirrhosis,and early and advanced hepatocellular carcinoma tissues and their diagnostic value in hepatocellular carcinoma:an immunohistochemical study[J].Med Sci Monit,2015,21:3209-3215.
[27] TAO Y,MESSER J S,GOSS K H,et al.HSP70 exerts oncogenic activity in the APC mutant min mouse model[J].Carcinogenesis,2016,37(7):731-739.
[28] POLIREDDY K,SINGH K,PRUSKI M,et al.Mutant P53R175H promotes cancer initiation in the pancreas by stabilizing HSP70[J].Cancer Lett,2019,453:122-130.
[29] ERIN E,BTTGER S.Cytoplasmic sequestration of the tumor suppressor P53 by a Heat Shock Protein 70 family member,mortalin,in human colorectal adenocarcinoma cell lines[J].Biochem Biophys Res Commun,2012,423(2):411-416.

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