光线性角化病向鳞状细胞癌转化的分子机制研究进展

摘要/Abstract

摘要：

光线性角化病（AK）是皮肤鳞状细胞癌（SCC）的癌前病变，AK向SCC转化的分子机制一直是研究热点，但尚未完全清楚。围绕染色体变异、基因突变、信号通路和其他因子机制4个部分，概述了染色体3p、9p、9q、13q、17p和17q基因选择性突变、18q杂合性缺失，p53、p16和Ras基因突变，转化生长因子β1信号通路、Fas/FasL信号通路活性异常，及基质金属蛋白酶因子异常表达在AK向SCC进展中的机制研究进展，为进一步研究提供参考。

Abstract:

Niu Ruixian, Xu Dan, He Li Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China Corresponding authors: He Li, Email: drheli2662@126.com; Xu Dan, Email: vivianxd@126.com 【Abstract】 Actinic keratosis （AK） is a precursor to cutaneous squamous cell carcinoma （SCC）, and molecular mechanisms of transformation from AK to SCC have been a research hotspot. This review focuses on four aspects of the molecular mechanisms, including chromosomal variation, gene mutations, signaling pathways and other factors, summarizes advances in selective mutations in chromosomes 3p, 9p, 9q, 13q, 17p and 17q, heterozygous deletion mutations in chromosome 18q, mutations of p53, p16 and Ras genes, abnormality of the transforming growth factor β1 signaling pathway and Fas/FasL signaling pathway, and aberrant expression of matrix metalloproteinases in the transformation from AK to SCC, which will provide a reference for further researches.

牛蕊仙徐丹何黎. 光线性角化病向鳞状细胞癌转化的分子机制研究进展[J]. 中华皮肤科杂志, 2016, 49(2): 144-146.doi:

参考文献 25

［1］	Werner RN, Sammain A, Erdmann R, et al. The natural history of actinic keratosis: a systematic review［J］. Br J Dermatol, 2013, 169（3）: 502⁃518. DOI: 10.1111/bjd.12420.
［2］	Ratushny V, Gober MD, Hick R, et al. From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma［J］. J Clin Invest, 2012, 122（2）: 464⁃472. DOI: 10. 1172/JCI57415.
［3］	Ashton KJ, Weinstein SR, Maguire DJ, et al. Chromosomal aberrations in squamous cell carcinoma and solar keratoses revealed by comparative genomic hybridization［J］. Arch Dermatol, 2003, 139（7）: 876⁃882.
［4］	Tomas D. Apoptosis, UV⁃radiation, precancerosis and skin tumors［J］. Acta Med Croatica, 2009, 63（2）: 53⁃58.
［5］	Neto PD, Alchorne M, Michalany N, et al. Reduced P53 staining in actinic keratosis is associated with squamous cell carcinoma: a preliminary study［J］. Indian J Dermatol, 2013, 58（4）: 325. DOI: 10.4103/0019⁃5154.113935.
［6］	Nindl I, Gottschling M, Krawtchenko N, et al. Low prevalence of p53, p16（INK4a） and Ha⁃ras tumour⁃specific mutations in low⁃graded actinic keratosis［J］. Br J Dermatol, 2007, 156（3）: 34⁃39.
［7］	胥兴文, 蒋亚辉, 杨和荣, 等. 日光性角化病与皮肤鳞状细胞癌临床相关性研究［J］. 四川医学, 2010, 31（5）: 621⁃622.
	Xu XW, Jiang YH, Yang HR, et al. Correlation study the clinical relevance of actinic keratoses and squamous cell carcinoma［J］.Sichuan Medical Journal, 2010, 31（5）: 621⁃622.
［8］	Choi KH, Kim GM, Kim SY. The keratin⁃14 in actinic keratosis and squamous cell carcinoma: is this a prognostic factor for tumor progression?［J］. Cancer Res Treat, 2010, 42（2）: 107⁃114. DOI: 10.4143/crt.2010.42.2.107.
［9］	Hodges A, Smoller BR. Immunohistochemical comparison of p16 in actinic keratoses and squamous cell carcinomas of the skin［J］. Mod Pathol, 2002, 15（11）: 1121⁃1125.
［10］	Kanellou P, Zaravinos A, Zioga M, et al. Genomic instability, mutations and analysis of the tumour suppressor genes p14（ARF）, p15（INK4b）, p16（INK4a） and p53 in actinic keratosis［J］. Cancer Lett, 2008, 264（1）: 145⁃161. DOI: 10.1016/j.canlet.2008.01.042.
［11］	Spencer JM, Kahn SM, Jiang W, et al. Activated ras genes occur in human actinic keratoses, premalignant precursors to squamous cell carcinomas［J］. Arch ermatol, 1995, 131（7）: 796⁃800.
［12］	Heldin CH, Miyazono K, ten Dijke P. TGF⁃beta signalling from cell membrane to nucleus through SMAD proteins［J］. Nature, 1997, 390（6659）: 465⁃471.
［13］	Massague J. TGFbeta in Cancer［J］. Cell, 2008, 134（2）: 215⁃230. DOI: 10.1016/j.cell.2008.07.001.
［14］	Chen YK, Yang SH, Huang AH, et al. Aberrant in multiple components of the transforming growth factor⁃beta1⁃induced Smad signaling pathway during 7,12⁃dimethylbenz［a］anthracene⁃induced hamster buccal⁃pouch squamous⁃cell carcinogenesis［J］. Oral Oncol, 2011, 47（4）: 262⁃267. DOI: 10. 1016/j.oraloncology.2011.02.003.
［15］	Roberts AB, Wakefield LM. The two faces of transforming growth factor beta in carcinogenesis［J］. Proc Natl Acad Sci U S A, 2003, 100（15）: 8621⁃8623.
［16］	Mordasky Markell L, Perez⁃Lorenzo R, Masiuk KE, et al. Use of a TGFbeta type I receptor inhibitor in mouse skin carcinogenesis reveals a dual role for TGFbeta signaling in tumor promotion and progression［J］. Carcinogenesis, 2010, 31（12）: 2127⁃2135. DOI: 10.1093/carcin/bgq191.
［17］	Xu D, Yuan R, Gu H, et al. The effect of ultraviolet radiation on the transforming growth factor beta 1/Smads pathway and p53 in actinic keratosis and normal skin［J］. Arch Dermatol Res, 2013, 305（9）: 777⁃786. DOI: 10.1007/s00403⁃013⁃1361⁃6.
［18］	Shao Y, Zhang J, Zhang R, et al. Examination of Smad2 and Smad4 copy⁃number variations in skin cancers［J］. Clin Transl Oncol, 2012, 14（2）: 138⁃142. DOI: 10.1007/s12094⁃012⁃0773⁃7.
［19］	杨开颜, 俞康, 李剑敏, 等. 鳞癌与基底细胞癌的Fas/FasL表达及其与细胞凋亡的关系［J］. 癌变·畸变·突变, 2003, 15（4）: 215⁃216.
	Yang KY, Yu K, Li JM, et al. The relationship between Fas/FasL in squamous cell carcinoma, basal cell carcinoma and cell apoptosis［J］. Carcinogenesis, Teratogenesis and Mutagenesis, 2003, 15（4）: 215⁃216.
［20］	Filipowicz E, Adegboyega P, Sanchez RL, et al. Expression of CD95 （Fas） in sun⁃exposed human skin and cutaneous carcinomas［J］. Cancer,2002, 94（3）: 814⁃819.
［21］	Satchell AC, Barnetson RS, Halliday GM. Increased Fas ligand by T cells and tumour cells in the progression of actinic keratosis to squamous cell carcinoma［J］. Br J Dermatol, 2004, 151（1）: 42⁃49.
［22］	徐丹, 刘彤云, 袁瑞红, 等.紫外线对光化性角化病和正常皮肤p53、基质金属蛋白酶2,9表达的影响［J］. 中华皮肤科杂志, 2013, 46（2）: 113⁃116. DOI: 10.3760/cma.j.issn.0412⁃2013.02.012.
	Xu D, Liu TY, Yuan RH, et al. Effect of ultraviolet radiation on the of p53, matrix metalloproteinase⁃2 and⁃9 in actinic keratosis lesions and normal human skin［J］. Chin J Dermatol, 2013, 46（2）: 113⁃116. DOI: 10.3760/cma.j.issn.0412⁃2013.02.012.
［23］	Tsukifuji R, Tagawa K, Hatamochi A, et al. Expression of matrix metalloproteinase⁃1, ⁃2 and ⁃3 in squamous cell carcinoma and actinic keratosis［J］. Br J Cancer, 1999, 80（7）: 1087⁃1091.
［24］	Poswar FO, Fraga CA, Farias LC, et al. Immunohistochemical analysis of TIMP⁃3 and MMP⁃9 in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma［J］. Pathol Res Pract, 2013, 209（11）: 705⁃709. DOI: 10.1016/j.prp.2013.08.002.
［25］	Zhu L, Kohda F, Nakahara T, et al. Aberrant of S100A6 and matrix metalloproteinase 9, but not S100A2, S100A4, and S100A7, is associated with epidermal carcinogenesis［J］. J Dermatol Sci, 2013, 72（3）: 311⁃319. DOI: 10.1016/j.jdermsci.2013.07.005.