| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Expression of E1AF/PEA3 (ETV4), an ets family transcriptional factor, has been implicated in invasive potential of several cancer cell lines through induction of matrix metalloproteinase (MMP) expression. The aim of this study was to examine E1AF mRNA expression and determine whether it is correlated with the progression and/or MMP expression in human colorectal cancer. Using the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we analyzed 100 colorectal cancer tissues for E1AF mRNA expression. Expression of ER81 (ETV1) and ERM (ETV5), the other 2 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 in vitro invasion assay were also performed. E1AF mRNA expression was detected in 62% of the 100 colorectal cancer tissues but was undetectable or only faintly detected in adjacent nontumorous tissues. E1AF mRNA was detected in
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all of the 10 liver metastatic tumor tissues from colorectal cancers. 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 cancer had significantly shorter overall and disease-free survival periods than did those with E1AF-negative cancer (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=0.0066 and P=0.0109, respectively). Among the expression of MMPs analyzed, expression of MMP-1 and matrilysin was significantly correlated with E1AF expression. In contrast, expression of ER81 and ERM was not correlated with clinicopathological characteristics or expression of these MMPs. Immunohistochemical expression of E1AF was predominantly observed at the invasive front, where the expression of MMP-1 and matrilysin and nuclear b-catenin expression were often colocalized. Less
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