The Tmp gene, encoding a membrane protein, is a c-Myc target with a tumorigenic activity

The c-Myc oncoprotein induces cell proliferation and transformation through its activity as a transcription factor. Uncovering the genes regulated by c-Myc is an essential step for understanding these processes. We recently i solated the tumor-associated membrane protein gene, Tmp, from a c-myc-induc ed mouse brain tumor. Here we show that Tmp is specifically highly expresse d in mammary tumors and T-cell lymphomas which develop in c-myc transgenic mice, suggesting that Tmp expression is a general characteristic of c-Myc-i nduced tumors. In addition, Tmp expression is induced upon serum stimulatio n of fibroblasts as shown in a time course closely correlated with c-myc ex pression. We have isolated the Tmp promoter region and identified a putativ e c-Myc binding element, CACGTG, located in the first intron of the gene. W e show here that constructs containing the Tmp regulatory region fused to a reporter gene are activated by c-Myc through this CACGTG element and that the c-Myc-Max protein complex can bind to this element. Moreover, an induci ble form of c-Myc, the MycER fusion protein, can activate the endogenous Tm p gene. We also show that Tmp-overexpressing fibroblasts induce rapidly gro wing tumors when injected into nude mice, suggesting that Tmp may possess a tumorigenic activity. Thus, TMP, a member of a novel family of membrane gl ycoproteins with a suggested role in cellular contact, is a c-Myc target an d is possibly involved in c-Myc-induced transformation.