CREST与MMP-2、MMP-9在乳腺癌侵袭转移中的作用及关系

Effect and relationship of CREST,MMP-2 and MMP-9 in the invasion and metastasis of breast cancer

目的观察钙反应性反式激活因子(CREST)、MMP-2、基质金属蛋白酶-9(MMP-9)在不同TNM分期乳腺癌组织中的表达及其与乳腺癌侵袭、转移的关系。方法乳腺癌组织90例,苏木素-伊红(HE)染色确定组织学类型、组织学分级,结合临床资料确定TNM分期,分为乳腺癌TNMⅠ期20例,Ⅱ期40例,Ⅲ期30例,分别应用免疫组织化学SP法检测CREST、MMP-2、MMP-9蛋白在乳腺癌组织不同TNM分期的表达;RT-PCR和Western印迹检测CREST在mRNA和蛋白水平的变化,分析三者的相关性及其与TNM分期的关系。结果 CREST、MMP-2、MMP-9蛋白在TNMⅢ期乳腺癌中的阳性表达率明显高于TNMⅠ、Ⅱ期,且在TNMⅡ期乳腺癌中的阳性表达率明显高于TNMⅠ(P均<0.05),且三者的表达呈正相关(P均<0.05)。CREST mRNA在TNMⅢ期乳腺癌中的相对表达量明显高于TNMⅠ、Ⅱ期,在TNMⅡ期乳腺癌中的相对表达量明显高于TNMⅠ(P均<0.05)。CREST和MMP-2、MMP-9的高表达均与分化程度有关(P均<0.05),而与患者的年龄无关(P>0.05)。结论乳腺癌中CREST、MMP-2、MMP-9的高表达可能与其侵袭、转移有关,联合检测三者的表达,对乳腺癌预后判断可能有指导作用。

Objective To observe the expressions of CREST,MMP-2 and MMP-9 in different TNM stage of breast cancer and explore the relationship with the invasion and metastasis of breast cancer. Methods Cases of breast cancer of TNM Ⅰ,Ⅱand Ⅲ stage were30%,40%,30% respectively. The expressions of CREST,MMP-2 and MMP-9 were evaluated in breast cancer tissues by immunohistochemistry,the expression of CREST mRNA was examined by RT-PCR,and Western blot was used to analyze the protein of CREST. Results The levels of CREST,MMP-2 and MMP-9 were overexpressed in breast cancer tissues. The expressions of CREST,MMP-2 and MMP-9 in TNM Ⅲ stage of breast cancer tissues were significantly higher than those in TNMⅠand Ⅱstage of breast cancer tissues( all P<0. 05). The overexpressions of CREST,MMP-2 and MMP-9 were dramatically associated with degree of differentiation( all P<0. 05),but were not associated with patients' age( all P<0. 05). Conclusions The overexpressions of CREST,MMP-2 and MMP-9 could be correlated with invasion and metastasis of breast cancer tissues,detection of the expressions of these three proteins might provide a new index for evaluating the prognosis of breast cancer.