解整合素-金属蛋白酶在乳腺癌中的表达下调及负性调节作用

Reduced expression of ADAM8 and its role in breast cancer

目的探讨解整合素一金属蛋白酶8（adisintegrin-like and metalloproteinase8，ADAM8）在乳腺癌组织中的表达及其在乳腺癌发生、发展中的作用。方法应用免疫组化（IHC），实时荧光定量聚合酶链反应（qRT-PCR），蛋白质印迹（Westernblot）等测定ADAM8在乳腺癌组织、乳腺正常组织的表达，分析其表达与乳腺癌临床病理因素的关系。结果ADAM8在乳腺癌组织和乳腺正常组织中均有表达，AD-AM8mRNA及蛋白水平在乳腺癌组织中的表达明显低于正常乳腺组织（qRT-PCR：P=0．015，IHC：P=0．044，Westernblot：P=0．000）。ADAM8表达率的高低与淋巴结转移、临床分期、肿瘤大小相关，但差异无统计学意义。免疫组化中Ⅲ＋Ⅳ期的阳性表达低于Ⅰ＋Ⅱ期（P=0．574）；qRT-PCR中Ⅱb＋Ⅲ期表达低于Ⅰ＋Ⅱa期（P=0．247）；有淋巴结转移的乳腺癌组织ADAM8表达低于无淋巴结转移组（IHC：P=0．560，qRT-PCR：P=0．592）。肿瘤〉2cm的ADAM8表达低于肿瘤≤2cm者，但差异无统计学意义。结论ADAM8在乳腺癌组织中表达下调，其程度与乳腺癌侵袭和转移性有关。ADAM8的负性表达可能在乳腺癌的发生发展中起调节作用。

Objective To investigate the expression of a disintegrin-like and metalloproteinase 8 （AD- AM8 ） in breast cancer and in normal breast tissues and its negative regulation role in tumorigenesis and progress of breast cancer. Methods The expression of ADAM8 in breast cancer and normal breast tissues was detected by immunohistochemistry （IHC）, qRT-PCR, and Western blot. The relation between ADAM8 expression and the clinicopathological parameters of breast cancer patients was analyzed. Results ADAM8 was expressed in breast cancer and normal breast tissues. The expression of ADAM8 mRNA and protein was significantly lower in breast cancer than in normal breast tissues （ qRT-PCR ： P = 0. 015, IHC ： P = 0. 044, Western blot ： P = 0. 000）. The ex- pression rate of ADAM8 was related to lymph node metastasis, tumor stage and tumor size, although the differ- ence had no statistical significance. IHC results showed that ADAM8 expression level was lower in stage Ⅲ＋Ⅳ than in stage Ⅰ＋Ⅱ （ P = 0. 574）. qRT-PCR showed ADAM8 mRNA expression was lower in stage Ⅱb ＋ Ⅲ than in stage Ⅰ＋Ⅱa （P = 0. 247）. ADAM8 expression was lower in the breast cancer tissues with lymph node metastasis than in those without lymph node metastasis （P = 0. 560 by IHC and P = 0. 592 by qRT-PCR）. AD- AM8 expression was lower in tumors whose size 〉2 cm than in tumors whose size≤2 cm, however, the differ- ence had no statistical significance （ P 〉 0.05 ）. Conclusions ADAM8 is significantly lower-expressed in breast cancer than in normal breast tissues, which is associated with clinical stages and lymph node metastasis. The re- duced expression of ADAM8 may play a role in the pathogenesis and progress of breast cancer.