P53、MDM2在基底细胞癌中的表达及意义
p53与MDM2在基底细胞癌发病过程中的相互关系：肿瘤的发生、发展较为复杂，其中涉及到原癌基因的激活和抑癌基因的失活以及二者之间的相互作用，本试验表明p53和MDM2表达升高在BCC发病过程中扮演着重要角色，由于BCC好发于老年人，推测在BCC发病过程中，长期的紫外线照射等诱因促使p53基因突变，突变型p53不能修复受损的DNA，DNA损伤后，激活MDM2并促使其表达，而MDM2降解突变型p53的能力减弱，导致突变型p53蛋白与MDM2蛋白的慢性蓄积，并反复加重此循环过程，最终引起细胞的恶性转化、增殖及肿瘤形成。在MDM2(+)/p53(-)病例，推测MDM2通过表达P90蛋白并与野生型p53蛋白结合，使野生型p53功能丧失，同样不能使受损的DNA恢复正常，而且，作为癌基因的MDM2，有可能与启动整个细胞周期的基因启动子结合，使细胞从G1期向S期转化，引起细胞成瘤性增强。由于BCC的发生、发展是一个多基因相互作用的复杂过程，在均无MDM2、p53表达的病例，可能有不依赖于二者的作用机制促进了BCC的发病，目前仍需要进一步的研究。
[参考文献]
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[2]Gorji H,Shahbazi N,Habibollahi P,et al.The glutathione-S-transferase P1 polymorphisms correlates with changes in expression of TP53 tumor suppressor in cutaneous basal cell carcinoma[J].J Dermatol Sci,2009,56(3):208-210.
[3]Adamkov M,Halasova E,Rajcani J,et al. Relation between expression pattern of p53 and survivin in cutaneous basal cell carcinomas[J]. Med Sci Monit,2011,17(3):74-80.
[4]Ansarin H,Daliri M,Soltani-Arabshahi R. Expression of p53 in aggressive and non-aggressive histologic variants of basal cell carcinoma[J]. Eur J Dermatol,2006,16(5):543-547.
[5]Weissman AM.Themes and variations on ubiquitylation[J].Nat Rev Mol Cell Biol, 2001,2(3):169-178.
[6]Momand J,Zambetti GP,Olson DC,et al.The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation[J].Cell,1992,69(7):1237-1245.
[7]Cho HS,Park EJ,Kim CW,et al.Immunohistochemical Study of p53 and MDM2 Expression on the Epithelial Tumors of the Skin[J]. Korean J Dermatol,2007,45(6):534-540.
[8]Almquist LM,Karagas MR,Christensen BC,et al.The role of TP53 and MDM2 polymorphisms in TP53 mutagenesis and risk of non-melanoma skin cancer[J].Carcinogenesis,2011,32(3):327-330.
[收稿日期]2012-03-06 [修回日期]2012-04-21
编辑/张惠娟, http://www.100md.com(艾东方 冯世军 马敬)
[参考文献]
[1]Shimizu M,Saitoh Y,Itoh H. Immunohistochemical staining of Ha-ras oncogene product in normal, benign, and m alignant human pancreatic tissues[J]. Hum Pathol,1990,21(6):607-612.
[2]Gorji H,Shahbazi N,Habibollahi P,et al.The glutathione-S-transferase P1 polymorphisms correlates with changes in expression of TP53 tumor suppressor in cutaneous basal cell carcinoma[J].J Dermatol Sci,2009,56(3):208-210.
[3]Adamkov M,Halasova E,Rajcani J,et al. Relation between expression pattern of p53 and survivin in cutaneous basal cell carcinomas[J]. Med Sci Monit,2011,17(3):74-80.
[4]Ansarin H,Daliri M,Soltani-Arabshahi R. Expression of p53 in aggressive and non-aggressive histologic variants of basal cell carcinoma[J]. Eur J Dermatol,2006,16(5):543-547.
[5]Weissman AM.Themes and variations on ubiquitylation[J].Nat Rev Mol Cell Biol, 2001,2(3):169-178.
[6]Momand J,Zambetti GP,Olson DC,et al.The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation[J].Cell,1992,69(7):1237-1245.
[7]Cho HS,Park EJ,Kim CW,et al.Immunohistochemical Study of p53 and MDM2 Expression on the Epithelial Tumors of the Skin[J]. Korean J Dermatol,2007,45(6):534-540.
[8]Almquist LM,Karagas MR,Christensen BC,et al.The role of TP53 and MDM2 polymorphisms in TP53 mutagenesis and risk of non-melanoma skin cancer[J].Carcinogenesis,2011,32(3):327-330.
[收稿日期]2012-03-06 [修回日期]2012-04-21
编辑/张惠娟, http://www.100md.com(艾东方 冯世军 马敬)