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Molecular and Cellular Biology, May 1999, p. 3529-3539, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Tmp Gene, Encoding a Membrane Protein, Is a c-Myc Target with a Tumorigenic Activity

Ittai Ben-Porath, Ofra Yanuka, and Nissim Benvenisty*

Department of Genetics, Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

Received 29 June 1998/Returned for modification 1 September 1998/Accepted 15 February 1999

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.

* Corresponding author. Mailing address: Department of Genetics, Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Phone: 972-2-6586774. Fax: 972-2-6586975. E-mail: nissimb{at}leonardo.ls.huji.ac.il.

Molecular and Cellular Biology, May 1999, p. 3529-3539, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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