p53在乳腺癌中的表达意义及5-氮杂脱氧胞苷对p53的调控作用

Expression of p53 in breast cancer and regulatory effects of 5-aza-2'-deoxycytidine on p53

目的 p53基因作为重要的抑癌基因,具有抑制肿瘤细胞增长、阻滞细胞周期及促进凋亡的作用,然而其在乳腺癌发生发展中的机制还有待进一步研究。文中研究p53在乳腺癌中的表达及其与临床病理参数的关系,进一步研究5-氮杂脱氧胞苷(5-aza-2'-deoxycytidine)在乳腺癌细胞中对p53表达调控的影响。方法采用免疫组化法检测组织芯片中80例乳腺癌组织及其癌旁正常组织中p53蛋白的表达情况,进一步用半定量RT-PCR及Western blot法检测乳腺癌细胞中p53的表达及5-氮杂脱氧胞苷对p53表达的影响。结果①p53在乳腺癌组织中的阳性表达率为41.25%,明显高于正常乳腺组织(22.5%),差异有统计学意义(P<0.01)。②p53的表达与乳腺癌病理分级、乳腺癌患者的年龄、临床分期及淋巴结转移差异无统计学意义(P>0.05)。③在乳腺癌细胞MCF-7中,p53 mRNA及蛋白表达均呈低表达状态;在5-氮杂脱氧胞苷作用后,其表达均上调。结论 p53在乳腺癌组织中高表达,可能在乳腺癌的发生发展中起重要的作用。5-氮杂脱氧胞苷可诱导p53高表达,使其发挥抑癌基因作用,从而为治疗p53低表达乳腺癌药物的研发提供依据。

Objective Tumor suppressor gene p53 can inhibit tumor cell growth,arrest cell cycle,and promote apoptosis.However,the effects of p53 on the pathogenesis of breast cancer have not been fully elucidated.The aim of this study was to explore the expression of p53 protein and the correlation with clinical pathologic features in breast cancer.Furthermore,the regulatory effects of 5-aza-2’-deoxycytidine on p53 in breast cancer cell line were also studied.Methods The expression of p53 protein in 80 cases of breast cancer and normal and adjacent tissue were determined by the immunohistochemical staining.The expressions of p53 mRNA and p53 protein in breast cancer cell line were determined by RT-PCR and Western blotting.Results The positive rate of p53 in breast cancer（ 41.25%） was higher than that in the normal and adjacent tissue（ 22.5%）（ P ＆lt;0.01）.The expression of p53 was not significantly correlated with age,grade,stage and lymph node metastasis（ P ＆gt;0.05）.The low expression of p53 both in mRNA and in protein levels were found in breast cancer cell line of MCF-7.The expression of p53 increased after 5-aza-2’-deoxycytidine administration.Conclusion p53 is highly expressed in breast cancer,which may play an important role in the development and progression of breast cancer.5-aza-2’-deoxycytidine,up-regulating the p53 expression in breast cancer cell line,which provides the evidents for the development of therapeutic drugs for the patients with low expression of p53 breast cancer.