The insulin receptor substrate 1 (IRS1) in intestinal epithelial differentiation and in colorectal cancer

Colorectal cancer (CRC) is associated with lifestyle factors that affect insulin/IGF signaling, of which the insulin receptor substrate 1 (IRS1) is a key transducer. We investigated expression, localization and pathologic correlations of IRS1 in cancer-uninvolved colonic epithelium, primary CRCs wit...

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Bibliographic Details
Published in:PloS one 2012-04, Vol.7 (4), p.e36190-e36190
Main Authors: Esposito, Diana L, Aru, Federica, Lattanzio, Rossano, Morgano, Annalisa, Abbondanza, Michela, Malekzadeh, Reza, Bishehsari, Faraz, Valanzano, Rosa, Russo, Antonio, Piantelli, Mauro, Moschetta, Antonio, Lotti, Lavinia Vittoria, Mariani-Costantini, Renato
Format: Article
Language:English
Subjects:
Adult
Aged
Analysis
Biology
c-Myc protein
Caco-2 Cells
Cancer
Cancer metastasis
Catenin
Cell Differentiation
Cell Polarity
Cell survival
Colon - cytology
Colon - metabolism
Colon - pathology
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Correlation
Differentiation
Epithelium
Familial adenomatous polyposis
Female
Gene Expression Regulation, Neoplastic
HT29 Cells
Humans
Insulin
Insulin receptor substrate 1
Insulin Receptor Substrate Proteins - genetics
Insulin Receptor Substrate Proteins - metabolism
Insulin-like growth factors
Intestinal Mucosa - cytology
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
Intestine
Kinases
Laboratories
Liver
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Liver Neoplasms - secondary
Localization
Male
Medicine
Metastases
mRNA
Mucosa
Mutation
Myc protein
p53 Protein
Pathology
Polarization
Protein Transport
RNA
Signaling
Spots
Staining
Tumor proteins
Tumors
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Summary:Colorectal cancer (CRC) is associated with lifestyle factors that affect insulin/IGF signaling, of which the insulin receptor substrate 1 (IRS1) is a key transducer. We investigated expression, localization and pathologic correlations of IRS1 in cancer-uninvolved colonic epithelium, primary CRCs with paired liver metastases and in vitro polarizing Caco2 and HT29 cells. IRS1 mRNA and protein resulted higher, relative to paired mucosa, in adenomas of familial adenomatous polyposis patients and in CRCs that overexpressed c-MYC, ß-catenin, InsRß, and IGF1R. Analysis of IRS1 immunostaining in 24 cases of primary CRC with paired colonic epithelium and hepatic metastasis showed that staining intensity was significantly higher in metastases relative to both primary CRC (P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0036190