Expression of the c-met Gene in Invasive Ductal Carcinomas / 한국유방암학회지

ABSTRACT

PURPOSE: The c-met protein, known as the hepatocyte growth factor (HGF) receptor, is a transmembrane 190 kDa heterodimer having tyrosine kinase activity, and it is encoded by the c-met oncogene. The HGF/c-met signaling pathway has been shown to demonstrate various cellular responses including mitogenic, proliferative, morphogenic and angiogenic activities. Although HGF and c-met are known to be expressed in a variety of organs and they play important roles in signal transduction, studies on its expression and its correlation to the clinicopathological parameters of breast cancer are very rare. METHODS: In this study, we examined the c-met mRNA and the c-met protein expression by utilizing RT-PCR and immunohistochemical methods for 50 cases of invasive ductal carcinomas (IDCs) and 20 cases of normal breast tissues. RESULTS: The c-met mRNA amplification was detected in 35 cases of IDCs (70%), but not in the normal tissues. The c-met protein overexpression was detected in 27 cases of IDCs (54%) and 2 cases of normal breast tissue (10%). Both the mRNA amplification and protein overexpression rates were significantly higher in tumor than in the normal breast tissue. The c-met mRNA amplification showed a tendency to increase in an invasive cancer and nodal metastasis. The c-met protein overexpression was significantly correlated with the well differentiated grade of tumor and it showed a tendency to decrease in the metastatic tumors. The concordance between both the mRNA amplification and protein expressions were not observed. CONCLUSION: These results suggest that the HGF/c-met signal pathway may be associated with the development of breast cancer. c-met mRNA amplification may play important roles both in tumor progression and metastasis. c-met protein overexpression may contribute to the morphogenesis of well-differentiated tumor.