乳腺浸润性导管癌中PTTG与MMP-2和MMP-9 的表达及相关性

垂体瘤转化基因（PTTG）具有促进体外细胞转化和体内致瘤的能力,在乳腺癌组织中高表达,并与乳腺癌的复发和淋巴结转移有关.但PTTG 能否通过调节基质金属蛋白酶(MMP-2、MMP-9) 调控乳腺癌的侵袭与转移尚不清楚.本研究证明，PTTG可能因促进乳腺癌细胞中 MMP-2、MMP-9 分泌而在乳腺癌细胞侵袭、转移中发挥重要作用.免疫组织化学 PV 9000 通用型两步法显示,60例乳腺浸润性导管癌组织中,PTTG、MMP-2 和 MMP-9表达定位于肿瘤细胞胞浆，阳性率与周围正常乳腺组织相比，差异均具有统计学意义(P＜0.05).三者阳性表达均与淋巴结转移及TNM分期有关(P＜0.05);与患者年龄、肿瘤大小等无关(P＞0.05).乳腺浸润性导管癌中PTTG分别与MMP-2、MMP-9的表达呈正相关(P＜0.05).小RNA干扰技术干扰乳腺癌细胞株 MDA-MB-231 中的PTTG，Western印迹结果显示，干扰组与对照组相比，PTTG、MMP-2 和 MMP-9蛋白的表达水平明显下降. Transwell 侵袭实验显示,干扰组肿瘤细胞体外侵袭能力明显降低(P＜0.01).本研究表明，PTTG可能通过促进乳腺癌细胞中 MMP-2、MMP-9分泌，促进乳腺癌细胞的侵袭、转移.

Expression and Relationship of PTTG,MMP-2 and MMP-9 in the Invasive Dutal Carcinoma of Breast

Pituitary tumor transforming gene (PTTG) is highly expressed in breast cancers and related to tumor migration and invasion. Besides promote transformation and induce tumorigenicity in vivo, whether PTTG expression has any connection with matrix metalloproteinase (MMP-2, MMP-9) remains elusive. Here, we reported that PTTG promoted breast cancer migration and invasion involved the activation of MMP-2 and MMP-9. PTTG, MMP-2 and MMP-9 expression in the cytoplasm was assayed by immunohistochemistry, with positivity of 75.0% (45/60), 73.3% (44/60) and 55.0% (33/60), respectively. The rates were significantly higher than those in normal breast tissue (P<0.05). The protein expression levels of PTTG, MMP-2 and MMP-9 were associated with lymph node metastasis and TNM stage (P<0.05), but not correlated with age, tumor size, or other clinicopathologic parameters (P>0.05)．PTTG and MMP-2, as well as PTTG and MMP-9, were positively correlated in invasive dutal carcinoma of breast (P<0.05)．When PTTG-siRNA was transfected into MDA-MB-231 cells, PTTG, MMP-2 and MMP-9 expression were reduced as detected by Western blotting. The adhesive ability decreased in transwell invasion assays compared with the transfections of controls (P<0.01)．It suggested that high expression of PTTG promoted the invasive and metastasis of dutal carcinoma of breast, involving the up regulating the expression of MMP-2, MMP-9.