title: Differentiation of Caco-2 cells requires both transcriptional and post-translational down-regulation of Myc.
abstract: Caco-2 cancer cell line is widely used to reproduce in vitro the differentiation of absorptive enterocytes of human intestinal epithelium. This cell line, when cultured over confluence for 21 days, spontaneously undergoes cell cycle arrest and differentiates with the formation of a polarized enterocyte-like monolayer. During this process, Myc protein is completely down-regulated, as occurs in normal enterocytes. Caco-2 cells differ from normal enterocytes for mutations of APC and β-catenin genes, factors known to be involved in the transcriptional control of MYC gene during enterocyte differentiation. In this paper, we investigated how Myc regulation could be achieved during Caco-2 differentiative process, notwithstanding the APC and β-catenin mutations. We highlighted the post translational regulation of Myc protein as one of the essential mechanisms that allows the exit from cell cycle and onset of differentiation of Caco-2 cells. Moreover, we found a strong correlation between Myc protein downregulation and the expression of the transcription factor Cdx2, suggesting the existence of a regulative link between these two proteins.
authors.affiliation: CNR, Istituto di Biologia Cellulare e Neurobiologia, Rome, Italy.
authors.forename: Bruno Daniele
authors.initials: BD
authors.lastname: Leoni
authors.forename: Manuela
authors.initials: M
authors.lastname: Natoli
authors.forename: Marta
authors.initials: M
authors.lastname: Nardella
authors.forename: Barbara
authors.initials: B
authors.lastname: Bucci
authors.forename: Flavia
authors.initials: F
authors.lastname: Zucco
authors.forename: Igea
authors.initials: I
authors.lastname: D'Agnano
authors.forename: Armando
authors.initials: A
authors.lastname: Felsani
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000254:growth & development; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin