Association of matrilysin mRNA expression with K-ras mutations and progression in pancreatic ductal adenocarcinomas.

Abstract

The matrix metalloproteinase matrilysin has been implicated in the progression of gastrointestinal and other cancers. The aim of this study was to examine matrilysin mRNA expression and determine whether it is correlated with K-ras mutations and/or progression of pancreatic carcinoma. Using the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we analyzed 11 pancreatic cancer cell lines and 70 pancreatic adenocarcinoma tissues for matrilysin mRNA expression. The results were correlated with clinicopathological characteristics and K-ras mutations. Significant amounts of matrilysin mRNA were detected in six of the eight cell lines with K-ras mutations but not in the three cell lines with wild-type K-ras. Matrilysin mRNA was detected in 57 (81.4% ) of the 70 tumor tissues and in all of the eight liver metastases, but not in any of the adjacent non-tumorous tissues. Matrilysin expression was significantly correlated with the size of tumor, tumor spreading, lymph node metastasis, advanced pathologic tumor-node- metastasis stage and K-ras mutations. The relative amounts of matrilysin mRNA in tumor tissues increased with increase in tumor stage and were highest in liver metastatic tumor tissues. Our results suggest that matrilysin, the expression of which is correlated with K-ras mutations, plays a key role in tumor growth and progression of pancreatic carcinoma.