Expression of ets-related transcriptional factor E1AF is associated with tumor progression and over-expression of matrilysin in human gastric cancer
Expression of ets-related transcriptional factor E1AF is associated with tumor progression and over-expression of matrilysin in human gastric cancer
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DOI：
10.1093/carcin/bgh011
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发表时间：
2004-03-01
期刊：
影响因子：
4.7
通讯作者：
Imai, K
中科院分区：
文献类型：
--
作者：
Yamamoto, H;Horiuchi, S;Imai, K
E1AF/PEA3 (ETV4)（一种 ets 家族转录因子）的表达通过诱导基质金属蛋白酶 (MMP) 表达与肿瘤进展有关。本研究的目的是检查 E1AF mRNA 表达并确定其是否与人类胃癌的进展和/或 MMP 表达相关。使用半定量逆转录聚合酶链式反应 (RT-PCR)，我们分析了 100 个胃癌组织的 E1AF mRNA 表达。还分析了 PEA3 亚家族的另外两个成员 ER81 (ETV1) 和 ERM (ETV5) 以及 Ets-1 和 Ets-2 的表达。结果与临床病理特征和MMP表达相关。还进行了免疫组织化学分析和体外侵袭测定。在100个胃癌组织中，64%检测到E1AF mRNA表达，但在邻近非肿瘤组织中检测不到或仅微弱检测到。 E1AF表达与浸润深度、淋巴管和静脉侵犯、淋巴结和远处转移、病理肿瘤-淋巴结-转移分期进展和复发显着相关。 E1AF 阳性肿瘤患者的总生存期和无病生存期显着短于 E1AF 阴性肿瘤患者（分别为 P < 0.0001 和 P < 0.0001）。在包括传统临床病理因素的多变量分析中，E1AF 表达保留了其对总体生存率和无病生存率的显着预测价值（分别为 P = 0.0082 和 P = 0.0096）。在分析的 MMP 中，基质溶素 (MMP-7) 的表达与 E1AF 的表达显着相关。 E1AF 的免疫组织化学表达主要在侵袭前沿观察到，其中基质溶解素的表达通常共定位。反义 E1AF 转染的 MKN45 胃癌细胞表达的基质溶素水平降低，并且体外侵袭性比模拟转染的 MKN45 细胞小。本研究结果提示，E1AF的表达与matrilysin的表达密切相关，在胃癌的进展中发挥着关键作用。
Expression of E1AF/PEA3 (ETV4), an ets family transcriptional factor, has been implicated in tumor progression through induction of matrix metalloproteinase (MMP) expression. The aim of this study was to examine E1AF mRNA expression and to determine whether it is correlated with progression of, and/or MMP expression in, human gastric cancer. Using the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we analyzed 100 gastric cancer tissues for E1AF mRNA expression. Expression of ER81 (ETV1) and ERM (ETV5), the other two members of the PEA3 subfamily, and Ets-1 and Ets-2 was also analyzed. The results were correlated with clinicopathological characteristics and MMP expression. Immunohistochemical analysis and an in vitro invasion assay were also performed. E1AF mRNA expression was detected in 64% of the 100 gastric cancer tissues, but was undetectable or only faintly detected in adjacent non-tumor tissues. E1AF expression was significantly correlated with depth of invasion, lymphatic and venous invasion, lymph node and distant metastasis, advance in pathological tumor-node-metastasis stage and recurrence. Patients with E1AF-positive tumors had significantly shorter overall and disease-free survival periods than did those with E1AF-negative tumors (P < 0.0001 and P < 0.0001, respectively). E1AF expression retained its significant predictive value for overall and disease-free survival in multivariate analysis that included conventional clinicopathological factors (P = 0.0082 and P = 0.0096, respectively). Among the MMPs analyzed, expression of matrilysin (MMP-7) was significantly correlated with E1AF expression. Immunohistochemical expression of E1AF was predominantly observed at the invasive front, where the expression of matrilysin was often co-localized. Antisense E1AF-transfected MKN45 gastric cancer cells expressed reduced levels of matrilysin and were less invasive in vitro than mock-transfected MKN45 cells. The results of this study suggest that E1AF, the expression of which is closely correlated with the expression of matrilysin, plays a key role in the progression of gastric cancer.