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2 results on '"Aru, F."'

1. The Insulin Receptor Substrate 1 (Irs1) in Intestinal Epithelial Differentiation and in Colorectal Cancer

Author

Faraz Bishehsari, Antonio Russo, Lavinia Vittoria Lotti, Reza Malekzadeh, Renato Mariani-Costantini, Rossano Lattanzio, Michela Abbondanza, Diana L. Esposito, Federica Aru, Annalisa Morgano, Mauro Piantelli, Rosa Valanzano, Antonio Moschetta, Esposito, DL, Aru, F, Lattanzio, R, Morgano, A, Abbondanza, M, Malekzadeh, R, Bishehsari, F, Valanzano, R, Russo, A, Piantelli, M, Moschetta, A, Lotti, LV, and Mariani-Costantini, R

Subjects
Male, Pathology, Anatomy and Physiology, Settore MED/06 - Oncologia Medica, Metastasis, Intestinal mucosa, Insulin Signaling Cascade, Molecular Cell Biology, Gastrointestinal Cancers, Basic Cancer Research, Insulin, Intestinal Mucosa, Insulin-like Growth Factor, COLON-CARCINOMA-CELLS, GROWTH-FACTOR RECEPTOR, BETA-CATENIN, FACTOR-I, IGF-I, NUCLEAR TRANSLOCATION, ADENOMATOUS POLYPOSIS, STEM-CELL, EXPRESSION, MUTATIONS, Multidisciplinary, biology, Chemistry, Liver Neoplasms, Cell Polarity, Cell Differentiation, Signaling Cascades, Gene Expression Regulation, Neoplastic, Protein Transport, medicine.anatomical_structure, Oncology, Medicine, Female, Colorectal Neoplasms, HT29 Cells, Research Article, Signal Transduction, Adult, endocrine system, medicine.medical_specialty, Colon, Science, IRS1, IGF1R, colorectal cancer, Endocrine System, Gastroenterology and Hepatology, Signaling Pathways, Familial adenomatous polyposis, medicine, Humans, Biology, Aged, Insulin-like growth factor 1 receptor, Endocrine Physiology, medicine.disease, digestive system diseases, Epithelium, IRS1, Insulin receptor, Insulin Receptor Substrate Proteins, biology.protein, Cancer research, Caco-2 Cells, Immunostaining, Insulin-Dependent Signal Transduction
Abstract

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

Published
2012

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

Author

Esposito DL, Aru F, Lattanzio R, Morgano A, Abbondanza M, Malekzadeh R, Bishehsari F, Valanzano R, Russo A, Piantelli M, Moschetta A, Lotti LV, and Mariani-Costantini R

Subjects
Adult, Aged, Caco-2 Cells, Cell Polarity, Colon cytology, Colon metabolism, Colon pathology, Colorectal Neoplasms genetics, Female, Gene Expression Regulation, Neoplastic, HT29 Cells, Humans, Intestinal Mucosa cytology, Liver Neoplasms genetics, Liver Neoplasms pathology, Liver Neoplasms secondary, Male, Protein Transport, Cell Differentiation, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Insulin Receptor Substrate Proteins genetics, Insulin Receptor Substrate Proteins metabolism, Intestinal Mucosa metabolism, Intestinal Mucosa pathology
Abstract

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<0.01) and colonic epithelium (P<0.01). Primary and metastatic CRCs, compared to colonic epithelium, contained significantly higher numbers of IRS1-positive cells (P = 0.013 and P = 0.014, respectively). Pathologic correlations in 163 primary CRCs revealed that diffuse IRS1 staining was associated with tumors combining differentiated phenotype and aggressive markers (high Ki67, p53, and ß-catenin). In Caco 2 IRS1 and InsR were maximally expressed after polarization, while IGF1R was highest in pre-polarized cells. No nuclear IRS1 was detected, while, with polarization, phosphorylated IRS1 (pIRS1) shifted from the lateral to the apical plasma membrane and was expressed in surface cells only. In HT29, that carry mutations constitutively activating survival signaling, IRS1 and IGF1R decreased with polarization, while pIRS1 localized in nuclear spots throughout the course. Overall, these data provide evidence that IRS1 is modulated according to CRC differentiation, and support a role of IRS1 in CRC progression and liver metastatization.

Published
2012
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