Regolazione dell’oncogene Myc nel differenziamento della linea Caco-2
Author(s)
Leoni, Bruno Daniele
Date Issued
February 20, 2009
Type
Doctoral Thesis
Abstract
The Caco-2 colon adenocarcinoma cell line spontaneously differentiates to a
small intestine phenotype after confluency. Little is known about the mechanisms that
regulate the differentiation process in this cell line bearing mutations on APC and β-
catenin. These mutations are usually associated with a constitutive upregulation of cellcycle-
related regulative genes as Myc or cyclin D1. Despite that, these cells are able to
exit from cell cycle after confluency and show an ordered transcriptional regulation of
specific genes. By the analysis at the RNA and protein level, we found that the β-catenin-
TCF transcriptional targets Myc and cyclin D1 are regulated differently during the
differentiation process. In particular we investigated the role of Myc regulation in Caco-2
differentiation.
In this work we show that a Myc complete downregulation is necessary for the
Caco-2 cells differentiation process and this is achieved through both a transcriptional
and a post translational regulation of the protein. The post-translational regulation is
based on the regulation of Myc degradation and requires the activity of the GSK3β kinase
on the Myc residue T58 in a cell cycle independent mechanism.
In addition, differentiated Caco-2 cells, upon wound of the monolayer, are able
to de-differentiate , proliferate again and show a renewed expression of Myc protein.
Additional information
Dottorato di ricerca in Genetica e biologia cellulare
Subjects
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