First Author | Ben-Porath I | Year | 1999 |
Journal | Mol Cell Biol | Volume | 19 |
Issue | 5 | Pages | 3529-39 |
PubMed ID | 10207076 | Mgi Jnum | J:54715 |
Mgi Id | MGI:1335737 | Doi | 10.1128/mcb.19.5.3529 |
Citation | Ben-Porath I, et al. (1999) The tmp gene, encoding a membrane protein, is a c-Myc target with a tumorigenic activity. Mol Cell Biol 19(5):3529-39 |
abstractText | 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 isolated the tumor-associated membrane protein gene, Tmp, from a c-myc-induced mouse brain tumor. Here we show that Tmp is specifically highly expressed 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-induced tumors. In addition, Tmp expression is induced upon serum stimulation of fibroblasts as shown in a time course closely correlated with c-myc expression. We have isolated the Tmp promoter region and identified a putative c-Myc binding element, CACGTG, located in the first intron of the gene. We 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 inducible form of c-Myc, the MycER fusion protein, can activate the endogenous Tmp gene. We also show that Tmp-overexpressing fibroblasts induce rapidly growing tumors when injected into nude mice, suggesting that Tmp may possess a tumorigenic activity. Thus, TMP, a member of a novel family of membrane glycoproteins with a suggested role in cellular contact, is a c-Myc target and is possibly involved in c-Myc-induced transformation. |