TRAIL up-regulation must be accompanied by a reciprocal PKCe down-regulation during differentiation of colonic epithelial cell: Implications for colorectal cancer cell differentiation
MetadataShow full item record
PKC isoenzymes play central roles in various cellular signalling pathways, participating in a variety of protein phosphorylation cascades that regulate/modulate cellular structure and gene expression. It has been firmly established that several isoforms of PKC have a role in the regulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) activity. Our interest in probing the role of the epsilon isoform of PKC in the colonic cell differentiation stems from the discovery that PKCε and TRAIL are involved in the differentiation of other cell types like hematopoietic stem cells. Although the role of PKCε and TRAIL in the gastrointestinal system is unclear, it has been observed that PKCε has oncogenic activity in colon epithelial cells (CEC), while TRAIL increases the death of intestinal epithelial cells during inflammation. Here we demonstrate a reciprocal expression of PKCε and TRAIL in human colon mucosa: CECs at the bottom of the colonic crypts show high levels of PKCε, being negative for TRAIL expression. On the contrary, luminal CECs are positive for TRAIL, while negative for PKCε. Indeed, TRAIL- and butyrate-induced differentiation of the human colorectal cancer cell line HT29 requires the decrease of PKCε expression, whose absence in turn increases cell sensitivity to TRAIL-induced apoptosis. Moreover, TRAIL preferentially promotes HT29 differentiation into goblet cells. Taken together, this data demonstrate that TRAIL and PKCε must be reciprocally regulated to ensure physiological CEC differentiation starting from the stem cell pool, and that the down-regulation of PKCε is however critical for the differentiation and apoptosis of cancer cells.
Showing items related by title, author, creator and subject.
A LuxRI-family regulatory system controls excision and transfer of the Mesorhizobium loti strain R7A symbiosis island by activating expression of two conserved hypothetical genesRamsay, Joshua; Sullivan, J.; Jambari, N.; Ortori, C.; Heeb, S.; Williams, P.; Barrett, D.; Lamont, L.; Ronson, C. (2009)The symbiosis island ICEM/SymR7A of Mesorhizobium loti R7A is an integrative and conjugative element (ICE) that carries genes required for a nitrogen-fixing symbiosis with Lotus species. ICEM/SymR7A encodes homologues ...
Analysis of candidate genes within the 3p14-p22 region of the human genome for association with bone mineral density phenotypesMullin, Benjamin H (2011)Previous studies have identified the 3p14-p22 chromosomal region as a quantitative trait locus for bone mineral density (BMD). The overall aim of this thesis is to identify the gene or genes from this region that are ...
Galli, D.; Gobbi, G.; Carrubbi, C.; Di Marcantonio, D.; Benedetti, L.; De Angelis, M.; Meschi, T.; Vaccarezza, Mauro; Sampaolesi, M.; Mirandola, P.; Vitale, M. (2013)Protein kinase Cepsilon (PKCε) exerts a well-known cardio-protective activity in ischemia–reperfusion injury and plays a pivotal role in stem cell proliferation and differentiation. Although many studies have been performed ...