Structure and inducible regulation of the human MET promoter

Giovanna Gambarotta, Sergio Pistoi, Silvia Giordano, Paolo M. Comoglio, Claudio Santoro

Research output: Contribution to journalArticlepeer-review

Abstract

The MET oncogene, encoding the tyrosine kinase receptor for the hepatocyte growth factor/scatter factor, is expressed in epithelial cells and overexpressed in a significant proportion of human epithelial cancers, suggesting the occurrence of transcriptional alteration(s). To identify the MET promoter, we isolated recombinant cDNA clones encompassing the entire 5'- noncoding sequence of MET messenger RNAs. Using probes derived from this region, we cloned the entire genomic region spanning the first MET exon and the flanking regulatory sequences. The first exon, containing the entire untranslated sequence, is present in the MET mRNAs of 7.1, 5.9, and 4.6 kilobases, showing that the expression of the multiple transcripts is regulated by a single promoter. The start site of transcription was determined by primer extension and by rapid amplification of cDNA ends. We show that a 300-base pair fragment, containing sequences upstream from the start site, efficiently drives the expression of a reporter gene in transfected epithelial cells. This promoter fragment also contains the cis- acting elements responsible for phorbol-ester induction.

Original languageEnglish
Pages (from-to)12852-12857
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number17
Publication statusPublished - Apr 29 1994

ASJC Scopus subject areas

  • Biochemistry

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