Therapeutic Research

Abstract

Toremifene（TOR）is a selective estrogen receptor modulator, and it is usually administered to patients with estrogen dependent breast cancer in a daily dose of 40 mg orally. However, when drug therapy, radiotherapy, etc., have become ineffective, TOR is administered to the patients in a daily dose of 120 mg orally. To elucidate the mechanisms of action of the high－dose TOR treatment, we evaluated action of TOR and its metabolites TOR－1, TOR－2, and TOR－4 on the MAPK signaling pathway of IGF－1 stimulated MCF－7 breast cancer cells. The results suggested that TOR and its metabolites suppress the IGF－1 stimulated cell growth of breast cancer by inhibiting phosphorylation of ERK1／2 protein in the MAPK pathway. These findings showed a novel molecular mechanism of high－dose TOR treatment to inhibit the growth of IGF－1 dependent breast cancer, especially emerging in recurrent cancer.