AP-2 MAY CONTRIBUTE TO IGF-II OVEREXPRESSION IN RHABDOMYOSARCOMA

The human insulin-like growth factor II gene is regulated in a develop ment-dependent manner and is not expressed in most adult tissues. Howe ver, high levels of insulin-like growth factor II mRNA are detected in many human tumors including rhabdomyosarcoma, an embryonal tumor of s keletal muscle origin. In this study, we demonstrate that the developm entally regulated transcription factor AP-2 is expressed at higher lev els in human fetal skeletal muscle and rhabdomyosarcoma cells compared to human adult skeletal muscle, Endogenous insulin-like growth factor II mRNA derived from the P3 as well as transfected P3 promoter activi ty were modestly and consistently increased to the same extent followi ng treatment of the rhabdomyosarcoma cell line RD with forskolin, a co mpound implicated in AP-2 transactivation, This effect of AP-2 on incr eased transcriptional activity was confirmed by nuclear run-on assays. Expression of AP-2B, a dominant-negative inhibitor of AP-2, suppresse d the P3 promoter activity in AP-2 expressing RD cells. Furthermore, f ive AP-2 protected regions corresponding to six AP-2 specific binding sites were detected in the insulin-like growth factor II P3 promoter. These data together suggest that AP-2 may contribute to the high expre ssion of IGF-II in rhabdomyosarcoma cells.