作者
潘翠瑜,李 欣
文章摘要
p53作为关键的抑癌基因,在维持基因组稳定性和调控细胞命运中发挥核心作用。高危型人乳头瘤病毒(HR-HPV)持续感染是宫颈癌发生的主要病因,其致癌蛋白E6通过靶向降解p53,解除细胞周期阻滞与凋亡防御,驱动宫颈上皮内瘤变(CIN)向浸润癌演进。本文系统综述了p53在宫颈癌前病变发生发展中的分子机制、表达特征及最新研究进展,旨在为宫颈病变的防治提供理论依据。
文章关键词
p53;宫颈上皮内瘤变(CIN);人乳头瘤病毒(HPV);E6蛋白;分子机制;生物标志物;靶向治疗
参考文献
[1] 张晨,李春明.TP53基因突变与口腔鳞状细胞癌预后的关系[J].现代肿瘤医学,2023,11:2169-2172.
[2] 陈廷安,赵凌燕,范文川,李星兵,江小林.p53及突变型p53蛋白表达与肺癌并发肺部感染的相关性[J].中国肿瘤外科杂志,2024,06:577-581.
[3] 郑诗祺,韩蕙如,琚璐,任国涛,王瑞芬,王立峰.Li-Fraumeni综合征相关肿瘤及研究进展[J].临床与实验病理学杂志,2025,03:369-373+379.
[4] 吴德轩,吴臻,王冬来.突变体p53的翻译后修饰与“功能获得”[J].中国生物化学与分子生物学报,2024,08:1043-1056.
[5] Gohler T,Bourdon JC.Gain-of-function p53 mutants:a new paradigm for cancer therapy?Trends Cancer,2019,5(6):375-388.
[6] Baugh EH,Ke H,Levine AJ,Bonneau RA,Chan CS.Why are there hotspot mutations in the TP53 gene in human cancers?Cell Death Differ.2018 Jan;25(1):154-160.
[7] Kastenhuber,E.R.and Lowe,S.W.(2017)Putting p53 in Context.Cell,170,1062-1078.
[8] Zhang X,Wen X,Peng R,Pan Q,Weng D,Ma Y,Zhang Y,Yang J,Men L,Wang H,Liang E,Wang C,Yang D,Zhang L,Zhai Y.A first- in-human phase I study of a novel MDM2/p53 inhibitor alrizomadlin in advanced solid tumors.ESMO Open.2024 Jul 11;9(8):103636.
[9] Bai,L.and Zhu,W.(2006)p53:Structure,Function and Therapeutic Application.Journal of Cancer Molecules,2,141-153.
[10] 邢益详,谢贞兰,刘晨.Beclin 1、p53及Ki-67在宫颈病变中表达及临床意义[J].慢性病学杂志,2019,20(12):1786-1788.
[11] 陆卉.p16INK4A、p53、Ki-67及ER在宫颈病变中表达的意义[J].实用妇科内分泌杂志(电子版),2018,19:118-119.
[12] Köbel M,Piskorz AM,Lee S,Lui S,LePage C,Marass F,Rosenfeld N,Mes Masson AM,Brenton JD.Optimized p53 immunohisto- chemistry is an accurate predictor of TP53 mutation in ovarian carcinoma.J Pathol Clin Res.2016 Jul 13;2(4):247-258.
[13] Köbel M,Kang EY.The Many Uses of p53 Immunohistochemistry in Gynecological Pathology:Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual9 Meeting.Int J Gynecol Pathol.2021;40(1):32-40.
[14] Perdrix A,Najem A,Saussez S,Awada A,Journe F,Ghanem G,Krayem M.PRIMA-1 and PRIMA-1Met(APR-246):From Mutant/Wild Type p53 Reactivation to Unexpected Mechanisms Underlying Their Potent Anti-Tumor Effect in Combinatorial Therapies.Cancers(Basel). 2017 Dec 16;9(12):172.
[15] Ye Huang,Wang Li,Yuke Zhou,Jinping Bai,Ning Li,Zhengding Su,Xiyao Cheng.Strategies for p53 Activation and Targeted Inhibitors of the p53-Mdm2/MdmX Interaction.[J].Cells,2025,148:.
[16] 李咏,许培箴,张蓉,等.重组人P53腺病毒注射液治疗宫颈鳞癌的近期疗效评价[J].基层医学论坛,2006,10(12A):1057-1060.
Full Text:
DOI