title: Integrin α1β1 expression is controlled by c-MYC in colorectal cancer cells.
abstract: The α1β1 collagen receptor is only present in a few epithelial cell types. In the intestine, it is specifically expressed in proliferating crypt cells. This integrin has been reported to be involved in various cancers where it mediates the downstream activation of the Ras/ERK proliferative pathway. We have recently shown that integrin α1β1 is present in two-thirds of colon adenocarcinomas, but the mechanism by which ITGA1 expression is regulated is not known. DNA methylation, involved in ITGA1 repression during megakaryocyte differentiation, is not the mechanism of ITGA1 regulation in colorectal cancer cells. Our in silico analysis of the ITGA1 promoter revealed two response elements for MYC, an oncogenic factor known to regulate cancer cell proliferation, invasion and migration. In situ, the expressions of both MYC and ITGA1 are localized in the lower crypt of the normal colon and correlate in 72% of the 65 analyzed colorectal cancers. MYC pharmacological inhibition or downregulation of expression with short hairpin RNA in HT29, T84 and SW480 cells resulted in reduced ITGA1 expression at both the transcript and protein levels. Chromatin immunoprecipitation assays revealed that MYC was bound to the chromatin region of the ITGA1 proximal promoter, whereas MYC overexpression enhanced ITGA1 promoter activity that was reduced with MAD co-transfection or by the disruption of the response elements. We concluded that MYC is a key regulating factor for the control of ITGA1 expression.
authors.affiliation: Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology, Université de Sherbrooke, Sherbrooke, QC, Canada.|Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Boudjadi
authors.affiliation: Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology, Université de Sherbrooke, Sherbrooke, QC, Canada.|Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: J C
authors.initials: JC
authors.lastname: Carrier
authors.affiliation: Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: J-F
authors.initials: JF
authors.lastname: Groulx
authors.affiliation: Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: J-F
authors.initials: JF
authors.lastname: Beaulieu
mesh_terms: D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D039222:Integrin alpha1beta1 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism / Q000502:physiology*
chemical_list: D039222:Integrin alpha1beta1; D016271:Proto-Oncogene Proteins c-myc