Ets up-regulates MET transcription

Giovanna Gambarotta, Carla Boccaccio, Silvia Giordano, Margherita Andǒ, Maria Cristina Stella, Paolo M. Comoglio

Research output: Contribution to journalArticle

Abstract

MET, a potentially harmful oncogene controlling invasive growth, is overexpressed in a significant percentage of human cancers. Since amplification of the MET gene occurs only in a fraction of these cases, we investigated the transcriptional mechanisms responsible for up-regulation of the promoter activity. The transcription driven by the 3.1 kbp DNA fragment containing the minimal promoter was studied by 5' progressive deletion analysis. The patterns of MET promoter activity suggest the presence of weak negative and positive elements in the region between 300 and 840 bp upstream to the transcription start site. The region encompassing the first regulates the promoter. This putative binding sites for members of the Ets transcription factor family, known to be involved in invasive growth. Transient co-expression of Ets1 resulted in a strong enhancement of the MET promoter activity. Increased expression of the Met protein was observed in cells stably transfected with ETS1. Double stranded oligonucleotides with Ets consensus sequence were used as a 'decoy' to inhibit binding to DNA native sites. They dramatically reduced the amount of Met protein in a human carcinoma cell line overexpressing the oncogene. Interestingly, Met activation induces transcription of ETS1 mRNA, showing that Ets proteins act both upstream and downstream to MET. These data indicate that members of the Ets family promote MET transcription and suggest their contribution to the invasive phenotype through overexpression of MET.

Original languageEnglish
Pages (from-to)1911-1917
Number of pages7
JournalOncogene
Volume13
Issue number9
Publication statusPublished - 1996

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Keywords

  • ETS transcription factors
  • HGF receptor
  • Proto-oncogenes

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Gambarotta, G., Boccaccio, C., Giordano, S., Andǒ, M., Stella, M. C., & Comoglio, P. M. (1996). Ets up-regulates MET transcription. Oncogene, 13(9), 1911-1917.