Ets transcription factors and human disease

Transformation of Madin-Darby canine kidney (MDCK) epithelial cells by Epstein-Barr virus latent membrane protein 1 (LMP1) induces expression of Ets1 and invasive growth

“…Ets1 is a member of Ets transcription factor family and recognizes speci®c nucleotides sequences with a GGAA/T core sequence (Dittmer and Nordheim, 1998). Physiologically, Ets1 is expressed in various mesodermal derivatives, such as endothelial cells and mesenchymal cells (Vandenbunder et al, 1989;Queva et al, 1993;Kola et al, 1993), but is also induced in dissociating epithelial cells, during epithelial-mesenchymal transitions occurring during early development and oncogenic transformation to acquire invasive features (Gilles et al, 1996;Fafeur et al, 1997).…”

Exon 4-encoded acidic domain in the epithelium-restricted Ets factor, ESX, confers potent transactivating capacity and binds to TATA-binding protein (TBP)

“…Members of the Ets family of transcription factors have been shown to play important roles in regulating gene programs critical for normal organismal development and cellular di erentiation, while fusion proteins involving Ets family members arising from chromosomal translocations are thought to account for a signi®cant fraction of all human leukemias and lymphomas as well as virtually all Ewings sarcomas and Primitive Neuro-Ectodermal Tumors (PNET), otherwise known as small round cell bone and soft tissue sarcomas of childhood (reviewed in Crepieux et al, 1994;Dittmer and Nordheim, 1998;Hromas and Klemsz, 1994;Sharrocks et al, 1997;Wasylyk and Nordheim, 1997).…”

Stromelysin-1 expression is activated in vivo by Ets-1 through palindromic head-to-head Ets binding sites present in the promoter

“…EBS are B9-bp sequences centered over a purine-rich 5 0 -GGAA/T-3 0 core motif bound by Ets proteins, important transcription factors involved in development and in several types of cancer and other human diseases (Dittmer and Nordheim, 1998;Maroulakou and Bowe, 2000;Trojanowska, 2000;Oikawa and Yamada, 2003). Several Ets proteins are able to stimulate the Stromelysin-1 promoter through this EBS palindrome: Ets-1 (Wasylyk et al, 1991), Ets-2 ( Buttice and Kurkinen, 1993) and Pea-3 (Higashino et al, 1995).…”