CRM1 Expression Is Associated with EGFR in Colorectal Carcinoma
AC Buckendahl, W Weichert, A Kasajima, C Denkert, M Dietel, A Noske. Charité University Hospital, Berlin, Germany; University Hospital, Zurich, Switzerland
Background: Chromosomal region maintenance/ exportin1 /Xpo1 (CRM1) is an important nuclear export factor for several proteins and mRNAs (e.g. p53, AKT, FOXO) relevant in tumor biology. Epidermal growth factor receptor (EGFR) belongs to the family of ErbB receptor tyrosine kinases and is deregulated in colorectal carcinomas and many other human tumors. Receptor activation stimulates several intracellular pathways that influence proliferation, cell migration, and survival. No data exists concerning the relation of CRM1 and EGFR in colorectal carcinomas to date. We aimed to investigate the expression patterns of CRM1 in colorectal cancer and to elucidate possible in vitro and in vivo interactions of CRM1 with EGFR.
Design: Expression of CRM1 was investigated by immunohistochemistry in 336 human colorectal carcinomas. Data was correlated to clinico-pathological factors, patient survival as well as to the expression levels of EGFR. CRM1 and EGFR protein levels in colon carcinoma cell lines were determined by western blotting. To investigate the role of CRM1 in the regulation of EGFR, colon cancer cell lines were incubated with Leptomycin B (LMB), a specific CRM1 inhibitor. EGFR expression patterns were analyzed by Western Blot and Immunofluorescence.
Results: Of the 336 colorectal carcinomas 143 cases (42.6%) showed nuclear CRM1 expression. Cytoplasmic staining was present in 127 cases (37.8%). No associations with clinico-pathological features and patient survival were found. High nuclear and cytoplasmic CRM1 expression was significantly associated with elevated EGFR protein levels. CRM1 as well as EGFR protein expression was observed in all investigated colon cancer cell lines. Inhibition of CRM1 in colon cancer cell lines resulted in a suppression of EGFR protein expression.
Conclusions: CRM1 is expressed in a subset of colorectal carcinomas and expression levels are related to EGFR expression in vivo. In vitro inhibition of CRM1 with LMB resulted in a suppression of EGFR protein expression. These data suggest a role for CRM1 in the regulation of EGFR expression in colorectal cancer.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 117, Tuesday Morning