Tamoxifen-induced cell death in malignant melanoma cells: possible involvement of the insulin-like growth factor-1 (IGF-1) pathway

Recent data indicate that the estrogen receptor (ER) blocker tamoxifen (TAM ) can induce cell death in malignant melanoma cells. However, as shown in t he present study and several other studies melanoma cells usually do not ex press classical ERs. In the present study we investigated whether the cytot oxic effect of TAM on melanoma cells could depend on interference with the expression or function of the insulin-like growth factor-1 receptor (IGF-1R ), a plasma membrane receptor important for cell survival in this tumor cel l type. Several melanoma cell lines were included in the analysis. Administ ration of TAM at a concentration of 15 mu m or more resulted in cell death of the melanoma cells within 48 h. TAM treatment was correlated to a slight to moderate inhibition of IGF-1 binding to IGF-IR. Since it has been repor ted that TAM can increase the release of IGF binding proteins (IGFBPs) we t hen investigated whether this mechanism could underly the decreased IGF-1 b inding. However, we could demonstrate that the amount of released IGFBPs we re unchanged or decreased in TAM-treated cells. Whereas TAM did not have an y strong effect on IGF-1 binding and the expression of IGF-IR at the cell s urface, it was was found to efficently block tyrosine phosphorylation of IC F-IR beta-subunit. Taken together, our data suggest that TAM-induced cytoto xicity of malignant melanoma cells can be due to inactivation of IGF-IR. (C ) 2000 Elsevier Science Ireland Ltd. All rights reserved.