Wnt信号通路中APC和Cyclin D1基因与卵巢癌关系的研究进展
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摘要
卵巢癌是女性最常见的恶性肿瘤之一,其发病率及死亡率逐年增加,虽然目前的治疗策略相对有效,但存在易复发及化疗耐药。卵巢癌的发生是一个多重因素作用、多步骤进展的过程,伴一系列致癌因素所致的基因突变和某些信号通路的异常激活。Wnt信号通路在哺乳动物胚胎的早期发育、器官形成、组织再生和其他生理过程中,具有至关重要的作用。如果这条信号通路中的关键调控基因发生突变,会导致其信号异常活化,就可能诱导恶变的发生发展。研究已表明,各种因素导致Wnt信号通路中的结肠腺瘤样息肉病蛋白(APC)基因的失活和细胞周期蛋白D1(Cyclin D1)基因的过度表达均与卵巢癌的发生发展有关。因此,探讨Wnt信号通路中的APC、Cyclin D1基因与卵巢癌的关系,有助于进一步揭示卵巢癌的发病机制,为卵巢癌的防治提供新的敏感检测指标和治疗靶点。本文就Wnt信号通路中APC、Cyclin D1基因与卵巢癌关系的研究进展作一综述。
引文
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[24] Liu W,Hua S,Dai Y,et al.Roles of Cx43 and AKAP95 in ovarian cancer tissues in G1/S phase[J].Int J Clin Exp Pathol,2015,8(11):14315-14324.
[25] Li Z,Cui J,Yu Q,et al.Evaluation of CCND1 amplification and CyclinD1 expression:diffuse and strong staining of CyclinD1 could have same predictive roles as CCND1 amplification in ER positive breast cancers[J].Am J Transl Res,2016,8(1):142-153.
[26] RuY,Chen XJ,Zhao ZW,et al.CyclinD1 and p57kip2 as biomarkers in differentiation,metastasis and prognosis of gastric cardia adenocarcinoma[J].Oncotarget,2017,8(43):73860-73870.
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[29] Liang S,Mu K,Wang Y,et al.CyclinD1,a prominent prognostic marker for endometrial diseases[J].Diagn Pathol,2013,8:138.
[30] Zhang B,Liu W,Li L,et al.KAI1/CD82 and CyclinD1 as biomarkers of invasion,metastasis and prognosis of laryngeal squamouscell carcinoma[J].Int J Clin Exp Pathol,2013,6(6):1060-1067.
[2] Zhou L,Graves M,MacDonald G,et al.Micrenvironmental regulation of BRCA1 gene expression by c-Jun and Fra2 in premalignant human ovarian surface epithelial cells[J].Mol Cancer Res,2013,11(3):272-281.
[3] Gatcliffe TA,Monk BJ,Planutis K,et al.Wnt signaling in ovarian tumorigenesis[J].Int J Gynecol Cancer,2008,18(5):954-962.
[4] 闫冰冰,李力.APC基因的DNA甲基化与卵巢癌关系荟萃分析[J].国际妇产科学杂志,2016,43(2):169-173.
[5] Feng Y,Sakamoto N,Wu R,et al.Tissue-specific effects of reduced β-catenin expression on adenomatous polyposis coli mutation-instigated Tumorigenesis in Mouse Colon and Ovarian Epithelium[J].PLoS Genet,2015,11(11):e1005638.
[6] Akalay I,Tan TZ,Kumar P,et al.Targeting WNT1-inducible signaling pathway protein 2 alters human breast cancer cell susceptibility to specific lysis through regulation of KLF-4 and miR-7 expression[J].Oncogene,2015,34(17):2261-2271.
[7] Saito-Diaz K,Chen TW,Wang X,et al.The way Wnt works:components and mechanism[J].Growth Factors,2013,31(1):1-31.
[8] Zhan T,Rindtorff N,Boutros M.Wnt signaling in cancer[J].Oncogene,2017,36(11):1461-1473.
[9] Yang K,Wang X,Zhang H,et al.The evolving roles of canonical WNT signaling in stem cells and tumorigenesis:implications in targeted cancer therapies[J].Lab Invest,2016,96(2):116-136.
[10] Aminuddin A,Ng PY.Promising druggable target in head and neck squamous cell carcinoma:Wnt Signaling[J].Front Pharmacol,2016,7:244.
[11] Mohammed MK,Shao C,Wang J,et al.Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal,tumorigenesis and cancer chemoresistance[J].Genes Dis,2016,3(1):11-40.
[12] Nagaraj AB,Joseph P,Kovalenko O,et al.Critical role of Wnt/β-catenin signaling in driving epithelial ovarian cancer platinum resistance[J].Oncotarget,2015,6(27):23720-23734.
[13] 何金水,黄轶群,翁剑鸣,等.β-catenin特异性抑制剂XAV939对套细胞淋巴瘤Jeko-1细胞增殖抑制的实验研究[J].中国实验血液学杂志,2015,23(2):411-415.
[14] Tian D,Shi Y,Chen D,et al.The Wnt inhibitor LGK-974 enhances radiosensitivity of HepG2 cells by modulating Nrf2 signaling[J].Int J Oncol,2017,51(2):545-554.
[15] Arend RC,Londoňo-Joshi AI,Gangrade A,et al.Niclosamide and its analogs are potent inhibitors of Wnt/β-catenin,mTOR and STAT3 signaling in ovarian cancer[J].Oncotarget,2016,7(52):86803.
[16] Li BQ,Liu PP,Zhang CH.Correlation between the methylation of APC gene promoter and colon cancer[J].Oncol Lett,2017,14(2):2315-2319.
[17] Hankey W,FrankelWL,Groden J.Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling:implications for therapeutic targeting[J].Cancer Metastasis Rev,2018,37(1):159-172.
[18] Schuijers J,Mokry M,Hatzis P,et al.Wnt-induced transcriptional activation is exclusively mediated by TCF/LEF[J].EMBO J,2014,33(2):146-156.
[19] Shen C,Sheng Q,Zhang X,et al.Hypermethylated APC in serous carcinoma based on a meta-analysis of ovarian cancer[J].J Ovarian Res,2016,9(1):60.
[20] 魏德娥,徐永萍.Wnt信号通路成分β-catenin和APC在卵巢肿瘤中的表达及意义[J].现代妇产科进展,2010,19(10):732-734.
[21] 肖琳.APC基因表达在上皮性卵巢癌发生发展中的作用及其分子机制的研究[D].重庆:重庆医科大学,2013.
[22] 毕玉婧.Anxa3,β-catenin,cyclinD1在上皮性卵巢癌中的表达及意义[D].泰安:泰山医学院,2015.
[23] Wang H,Wang H,Makki MS,et al.Overexpression of β-catenin and cyclinD1 predicts a poor prognosis in ovarian serous carcinomas[J].Int J Clin Exp Pathol,2014,7(1):264-271.
[24] Liu W,Hua S,Dai Y,et al.Roles of Cx43 and AKAP95 in ovarian cancer tissues in G1/S phase[J].Int J Clin Exp Pathol,2015,8(11):14315-14324.
[25] Li Z,Cui J,Yu Q,et al.Evaluation of CCND1 amplification and CyclinD1 expression:diffuse and strong staining of CyclinD1 could have same predictive roles as CCND1 amplification in ER positive breast cancers[J].Am J Transl Res,2016,8(1):142-153.
[26] RuY,Chen XJ,Zhao ZW,et al.CyclinD1 and p57kip2 as biomarkers in differentiation,metastasis and prognosis of gastric cardia adenocarcinoma[J].Oncotarget,2017,8(43):73860-73870.
[27] Du B,Wang Z,Zhang X,et al.MicroRNA-545 suppresses cell proliferation by targeting cyclin D1 and CDK4 in lung cancer cells[J].PLoS One,2014,9(2):e88022.
[28] Yamamoto K,Lee BJ,Li C,et al.Early B-cell-specific inactivation of ATM synergizes with ectopic CyclinD1 expression to promote pre-germinal center B-cell lymphomas in mice[J].Leukemia,2015,29(6):1414-1424.
[29] Liang S,Mu K,Wang Y,et al.CyclinD1,a prominent prognostic marker for endometrial diseases[J].Diagn Pathol,2013,8:138.
[30] Zhang B,Liu W,Li L,et al.KAI1/CD82 and CyclinD1 as biomarkers of invasion,metastasis and prognosis of laryngeal squamouscell carcinoma[J].Int J Clin Exp Pathol,2013,6(6):1060-1067.