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 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 inten…
Abstract 3897: Sam68 sustains self-renewal and invasiveness of breast cancer initiating cells
Abstract Background: Breast cancer is the leading worldwide cause of death among women due to the high metastatic spread of this disease. As by definition, Cancer Initiating Cells (CICs) are a fraction of primary tumor cells harboring tumorigenic potential and successful outgrowth at metastatic sites. Targeting molecular events affecting CICs peculiarities, as self-renewal and an innate chemoresistance, could improve the ineffectiveness of current therapies. Sam68, the major CD44 splicing regulator, is a multifunctional RNA-binding protein involved in multiple steps of RNA metabolism and its expression is aberrant in breast cancer. Herein, we highlight novel implications of Sam68 in the mam…
Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatellite instability status and country of origin
Background: K-ras mutations are a key step in colorectal cancer progression. Such mutations have been widely studied in case series from Western countries but there are few data on the rate and spectrum of mutations in tumors from countries where the epidemiological features of the disease are different. Patients and methods: Tumor samples from 182 Iranian colorectal cancer patients (170 sporadic cases and 12 HNPCC cases) were screened for K-ras mutations at codons 12, 13 and 61 by sequencing analysis. The cases were also characterized for microsatellite instability at mononucleotide repeats by PCR and fragment analysis, and classified according to microsatellite instability status. The fre…