Expression of NHERF1 in Colonic Tumors Induced by

Authors: Mariana Troncoso F Darío Cuello Carrión Elina Guiñazu Mariel A Fanelli Magdalena MonttGuevara Rómulo L Cabrini Rubén W Carón Erica L Kreimann

Publish Date: 2011/07/06

Volume: 2, Issue: 4, Pages: 214-

PDF Link

Abstract

In normal embryonic fibroblasts the Na+/H+ exchanger regulator factor 1 NHERF1 stabilizes Ecadherin/βcatenin binding and the lack of NHERF1 expression promotes cell transformation thus acting as a tumor suppressor gene We here tested the hypothesis that NHERF1 could act as a tumor suppressor gene in colon cancer as a mediator of estrogens’ protective actions in colon carcinogenesis We studied the expression and localization of NHERF1 and βcatenin by immunohistochemistry in colonic tumors induced by 12 dimethylhidrazine DMH in Sprague–Dawley rats One group of the rats treated with the carcinogen was ovariectomized OVX in the middle of the tumor induction simulating a human menopausal condition We observed a protective role of estrogens in colon cancer as nonovariectomized rats DMH had a reduced tumor area compared with the ovariectomized group DMH + OVX mean ± SE 2898 ± 465 vs 6758 ± 869 p  000380 Despite the lack of plasma estrogen stimulation we found abundant expression of NHERF1 in colon tumors from ovariectomized rats NHERF1 was mainly localized in the cytoplasm of the adenocarcinoma cells and lost the apical localization previously reported in normal colon tissue We also detected expression of NHERF1 by western blot in the SW48 CACO2 and HT29 colon cancer cell lines Nonestrogenic factors in plasma or the tumor microenvironment may regulate NHERF1 expression in transformed colon epithelial cells Further studies are required to understand the regulation of NHERF1 expression in colon cancer tissueThis work was supported by the National Research Council of Argentina CONICET We thank Juan Rosales and Andrea LafallaManzano for their technical assistance and Susana R Valdez for her valuable suggestions in the preparation of the manuscript We thank Paul Strobl for his contribution in the editing of this manuscript

Keywords: