Expression of NHERF1 in Colonic Tumors Induced by 1,2-dimethylhydrazine in Rats is Independent of Plasma Ovarian Steroids

被引：5
作者：
Troncoso M. [1 ]
Cuello Carrión F.D. [1 ]
Guiñazu E. [3 ]
Fanelli M.A. [1 ]
Montt-Guevara M. [2 ]
Cabrini R.L. [4 ,5 ]
Carón R.W. [3 ]
Kreimann E.L. [5 ]
机构：
[1] Laboratory of Oncology, Institute of Experimental Medicine and Biology of Cuyo, Scientific and Technological Center of Mendoza (CCTMza), National Research Council of Argentina (CONICET), Mendoza CP 5500, Av. Ruiz Leal s/n Parque General San Martín
[2] Laboratory of Tumor Biology, Institute of Experimental Medicine and Biology of Cuyo (IMBECU), Scientific and Technological Center of Mendoza (CCTMza), National Research Council of Argentina (CONICET), Mendoza CP 5500, Av. Ruiz Leal s/n Parque General San M
[3] Laboratory of Hormones and Cancer Biology, Institute of Experimental Medicine and Biology of Cuyo, Scientific and Technological Center of Mendoza (CCTMza), National Research Council of Argentina (CONICET), Mendoza CP 5500, Av. Ruiz Leal s/n Parque General
[4] Department of Oral Pathology, School of Dentistry, University of Buenos Aires, Buenos Aires
[5] Department of Radiobiology, National Atomic Energy Commission of Argentina (CNEA), B1650KNA Buenos Aires, Av. General Paz 1499, San Martín
来源：
Hormones and Cancer | 2011年 / 2卷 / 4期
关键词：
Colon cancer; Estrogens; NHERF1/EBP50; Ovariectomy; Rat;
D O I：
10.1007/s12672-011-0075-5
中图分类号：
学科分类号：
摘要：
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. © 2011 Springer Science+Business Media, LLC.
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页码：214 / 223
页数：9
相关论文
共 52 条
[1]  
Arai N., Strom A., Rafter J.J., Gustafsson J.A., Estrogen receptor beta mRNA in colon cancer cells: growth effects of estrogen and genistein, Biochem Biophys Res Commun, 270, pp. 425-431, (2000)
[2]  
Belov L., Zhou J., Christopherson R.I., Review cell surface markers in colorectal cancer prognosis, Int J Mol Sci, 12, pp. 78-113, (2011)
[3]  
Bretscher A., Chambers D., Nguyen R., Reczek D., ERM-merlin and EBP50 protein families in plasma membrane organization and function, Annu Rev Cell Dev Biol, 16, pp. 113-143, (2000)
[4]  
Bu Z., Callaway D.J.E., Proteins move! Protein dynamics and long-range allostery in cell signaling, Adv Protein Chem Struct Biol, 83, pp. 163-221, (2011)
[5]  
Cagir B., Nagy M.W., Topham A., Rakinic J., Fry R.D., Adenosquamous carcinoma of the colon, rectum, and anus: epidemiology, distribution, and survival characteristics, Dis Colon Rectum, 42, pp. 258-263, (1999)
[6]  
Calle E.E., Miracle-McMahill H.L., Thun M.J., Heath Jr. C.W., Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women, J Natl Cancer Inst, 87, pp. 517-523, (1995)
[7]  
Cavallaro U., Christofori G., Cell adhesion and signalling by cadherins and Ig-CAMs in cancer, Nat Rev Cancer, 4, 2, pp. 118-132, (2004)
[8]  
Cuello-Carrion F.D., Troncoso M., Guinazu E., Valdez S.R., Fanelli M.A., Ciocca D.R., Kreimann E.L., Estrogens regulate the expression of NHERF1 in normal colon during the reproductive cycle of Wistar rats, Hist Cell Biol Hist Cell Bio, 134, 6, pp. 623-630, (2010)
[9]  
de Castro-Carpeno J., Belda-Iniesta C., Casado Saenz E., Hernandez Agudo E., Feliu Batlle J., Gonzalez Baron M., EGFR and colon cancer: A clinical view, Clin Transl Oncol, 10, pp. 6-13, (2008)
[10]  
Devlin H.L., Mudryj M., Progression of prostate cancer: multiple pathways to androgen independence, Cancer Lett, 18, 2, pp. 177-186, (2009)
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