title: Expression of NHERF1 in colonic tumors induced by 1,2-dimethylhydrazine in rats is independent of plasma ovarian steroids.
abstract: In normal embryonic fibroblasts, the Na(+)/H(+) exchanger regulator factor 1 (NHERF1) stabilizes E-cadherin/β-catenin 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 β-catenin by immunohistochemistry in colonic tumors induced by 1,2 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 non-ovariectomized rats (DMH) had a reduced tumor area compared with the ovariectomized group (DMH + OVX; mean ± SE) 28.98 ± 4.65 vs. 67.58 ± 8.69 (p < 0.00380). 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, CACO-2, and HT29 colon cancer cell lines. Non-estrogenic 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 tissue.
authors.affiliation: Laboratory of Oncology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU), Scientific and Technological Center of Mendoza (CCTMza), National Research Council of Argentina (CONICET), Av. Ruiz Leal s/n Parque General San Martín, Mendoza CP 5500, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Troncoso
authors.forename: F Darío
authors.initials: FD
authors.lastname: Cuello Carrión
authors.forename: Elina
authors.initials: E
authors.lastname: Guiñazu
authors.forename: Mariel A
authors.initials: MA
authors.lastname: Fanelli
authors.forename: Magdalena
authors.initials: M
authors.lastname: Montt-Guevara
authors.forename: Rómulo L
authors.initials: RL
authors.lastname: Cabrini
authors.forename: Rubén W
authors.initials: RW
authors.lastname: Carón
authors.forename: Erica L
authors.initials: EL
authors.lastname: Kreimann
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D002273:Carcinogens / Q000633:toxicity; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D016147:Genes, Tumor Suppressor; D012739:Gonadal Steroid Hormones / Q000097:blood*; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D010052:Ovariectomy; D010750:Phosphoproteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis*
chemical_list: D002273:Carcinogens; D012739:Gonadal Steroid Hormones; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D019813:1,2-Dimethylhydrazine