205P - Significance of c-MET as a therapeutic target in triple-negative breast cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Breast Cancer
Translational Research
Presenter Shinichiro Kashiwagi
Authors S. Kashiwagi1, M. Yashiro1, N. Aomatsu1, H. Kawajiri1, T. Takashima2, N. Onoda1, T. Ishikawa1, K. Hirakawa1
  • 1Surgical Oncology, Osaka City University Graduate School of Medicine, 545-8585 - Osaka/JP
  • 2Dept. Surgical Oncology, Osaka City University Graduate School of Medicine, 545-8585 - Osaka/JP



The molecular and biological mechanisms of cancer proliferation and metastasis are being elucidated. Therapies targeting the biological characteristics of various cancers have been adopted. Hormone therapy, molecular target therapy, etc., are chosen depending on against estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expressions in breast cancer. However, no effective therapy is available for ER-, PR-, and HER2-negative triple-negative breast cancer (TNBC) because their targets are unknown. c-met tyrosine kinase receptor for Hepatocyte growth factor (HGF) has attracted attention as a novel molecular target of cancer therapy. The c-met receptor for HGF is involved in the migration, invasion, and proliferation of cancer cells. The activation mechanisms of c-met include the overexpression, amplification, and mutation of the met gene, as well as ligand binding. Increased c-met protein expression, including coexpression with its ligand HGF, is observed in various cancers. Reportedly, the prognosis of breast cancer is correlated with HGF/c-met coexpression and c-met overexpression. c-met signaling plays an important role in the proliferation of breast cancer cells. However, few reports have been published regarding their correlation with TNBC.

Material and methods

A total of 1,036 patients who had undergone resection of a primary breast cancer at our institute were enrolled. ER / PR / HER2 status and c-met expression were assessed by immunohistochemistry. In vitro study, TNBC cell lines, MDA-MB 231 and OCUB-2, and non-TNBC cell lines, MCF-7 and OCUB-1, were used. c-met mRNA expression was examined by RT-PCR. Then, the effects of HGF, c-met siRNA, and c-met inhibitors on the proliferation of breast cancer cell lines were examined.


The 1,036 patients included 190 TNBC patients, whose prognoses were poorer than those of non-TNBC patients. In the TNBC patients, the c-met expression-positive group showed a poorer prognosis than the control group. c-met was expressed in the TNBC cell lines, whose proliferation was enhanced by HGF. c-met kinase inhibitors and c-met siRNA inhibited the proliferation of TNBC cell lines.


c-met expression is a potential molecular target and useful in classifying TNBC.


All authors have declared no conflicts of interest.