Book of abstract 2008

TAF12 is regulated by ras, to mediate the alteration of E-cadherin
expression in epithelial-to-mesenchymal transition (EMT) (1)
Angeliki Voulgari1, Stella Voskou1, Làszlò Tora2, Irwin Davidson2, Alexander Pintzas1
1National Hellenic Research Foundation, Institute of Biological Research and Biotechnology, Athens;
2Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg
Activating mutations in the RAS proto-oncogene result in alteration of gene expression
leading to tumorigenesis (2). The TFIID complex, composed of the TATA box-binding
protein (TBP) and its associated factors (TAFs), regulates the initiation of transcription.
TFIID components are altered by cellular signals to specifically redirect transcription.
Notably, TBP is regulated by Ras to allow full cellular transformation. To investigate
further links between TFIID and the RAS-induced carcinogenesis, we monitored the
expression of TBP and TAF in human colon carcinoma cells (1). We identified TAF12
levels as being up-regulated in cell lines bearing natural RAS mutations and having some
epithelial to mesenchymal transition (EMT) characteristics. TAF12 expression was further
enhanced via a MEK-dependent mechanism, in an EMT-model cell line obtained after
stable overexpression of a mutated RAS isoform in Caco-2 cells (2). We also showed in vivo
and in vitro that the ETS1 protein was involved in the up-regulation of TAF12 expression
during RAS transformation. Interestingly, reduction of TAF12 levels by siRNA enhanced
E-cadherin mRNA and protein levels and reduced migration and adhesion properties of
RAS transformed cells with EMT (1-3). Overall, our study indicates the importance of
TAF12 in the process of Ras-induced transformation properties of human colon cells,
most notably those related to increased motility, by specifically regulating expression of
E-cadherin.
References:
1. Voulgari et al., under revision
2. Roberts ML, Drosopoulos KG, Vasileiou I, Stricker M, Taoufik E, Maercker C, Guialis A, Alexis MN,
Pintzas A., 2006, Int J Cancer
3. Andreolas C, Kalogeropoulou M, Voulgari A, Pintzas A., 2007, Int J Cancer
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