nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.10.2009 | Original Paper

Expression of anion exchanger 1 is associated with tumor progress in human gastric cancer

verfasst von: Wei-Qing Xu, Ling-Jun Song, Qiang Liu, Lei Zhao, Lin Zheng, Zhao-Wen Yan, Guo-Hui Fu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2009

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Anion exchanger 1 (AE1) is a transmembrane glycoprotein which is abundantly expressed in erythrocyte plasma membrane and mediates the electroneutral exchange of Cl⁻ and HCO₃ ⁻. We previously reported that the AE1 protein was unexpectedly expressed in the gastric and colonic cancer and take part in the carcinogenesis of the cancer cells. The aim of the present study is to determine the potential clinical implications of AE1 expression in gastric carcinoma.

Methods

Immunohistochemistry assay was used to determine the expression of AE1 protein. The expression of AE1 in normal and malignant tissues from 286 patients with early and advanced gastric carcinoma was examined. The correlations of AE1 expression with clinicopathological parameters, including age, tumor size, location and subtypes, expression frequency, survival period and lymph metastasis were assessed by Chi-squared test and t test analysis.

Results

AE1 immunoreactivity was negative in normal gastric tissue. Positive immunostaining of AE1 was detected in gastric carcinoma regardless of the location. AE1 was most frequently expressed in the gastric antrum carcinoma compared with gastric body cancer (P = 0.034). Expression of AE1 was significantly associated with bigger tumor size, deeper invasion, shorter survival period, and non-lymph metastasis. In para-cancer tissues of intestinal-type gastric cancer, the expression frequency of AE1 was higher than that in diffuse-type (P = 0.011).

Conclusion

The results showed a strong association of AE1 expression with the onset and progression of the gastric cancer and that may be helpful for improving the tumor classification and the treatment of cancer.

Akel A, Wagner CA, Kovacikova J, Kasinathan RS, Kiedaisch V, Koka S, Alper SL, Bernhardt I, Wieder T, Huber SM, Lang F (2007) Enhanced suicidal death of erythrocytes from gene-targeted mice lacking the Cl⁻/HCO₃ ⁻ exchanger AE1. Am J Physiol Cell Physiol 292(5):C1759–C1767. doi:10.1152/ajpcell.00158.2006 CrossRefPubMed

Alper SL (2006) Molecular physiology of SLC4 anion exchangers. Exp Physiol 91(1):153–161. doi:10.1113/expphysiol.2005.031765 CrossRefPubMed

Alper SL, Darman RB, Chernova MN, Dahl NK (2002) The AE gene family of Cl⁻/HCO₃ ⁻ exchangers. J Nephrol 15:S41–S53PubMed

Argani P, Choti MA, Abraham SC (2007) Achlorhydria, parietal cell hyperplasia, and multiple gastric carcinoids: a new disorder. Am J Surg Pathol 31(3):488. doi:10.1097/01.pas.0000213405.95440.a1 CrossRefPubMed

Argent RH, Thomas RJ, Aviles-Jimenez F, Letley DP, Limb MC, El-Omar EM, Atherton JC (2008) Toxigenic Helicobacter pylori infection precedes gastric hypochlorhydria in cancer relatives, and H. pylori virulence evolves in these families. Clin Cancer Res 14(7):2227–2235. doi:10.1158/1078-0432.CCR-07-2022 CrossRefPubMed

Bruce LJ (2008) Red cell membrane transport abnormalities. Curr Opin Hematol 15(3):184–190. doi:10.1097/MOH.0b013e3282f97b0a CrossRefPubMed

Ernst M, Najdovska M, Grail D, Lundgren-May T, Buchert M, Tye H, Matthews VB, Armes J, Bhathal PS, Hughes NR, Marcusson EG, Karras JG, Na S, Sedgwick JD, Hertzog PJ, Jenkins BJ (2008) STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J Clin Invest 118(5):1727–1738PubMed

Friis-Hansen L (2006) Achlorhydria is associated with gastric microbial overgrowth and development of cancer: lessons learned from the gastrin knockout mouse. Scand J Clin Lab Invest 66(7):607–621. doi:10.1080/00365510600873894 CrossRefPubMed

Fu GH, Wang Y, Xi YH, Shen WW, Pan XY, Shen WZ, Jiang XS, Chen GQ (2005) Direct interaction and cooperative role of tumor suppressor p16 with band 3 (AE1). FEBS Lett 579:2105–2110. doi:10.1016/j.febslet.2005.02.063 CrossRefPubMed

Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M (2008) Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet 372(9636):392–397. doi:10.1016/S0140-6736(08)61159-9 CrossRefPubMed

Gawenis LR, Ledoussal C, Judd LM, Prasad V, Alper SL, Stuart-Tilley A, Woo AL, Grisham C, Sanford LP, Doetschman T, Miller ML, Shull GE (2004) Mice with a targeted disruption of the AE2 Cl⁻/HCO₃ ⁻ exchanger are achlorhydric. J Biol Chem 279(29):30531–30539. doi:10.1074/jbc.M403779200 CrossRefPubMed

Gravalos C, Jimeno A (2008) HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 19(9):1523–1529. doi:10.1093/annonc/mdn169 CrossRefPubMed

Ito D, Koshino I, Arashiki N, Adachi H, Tomihari M, Tamahara S, Kurogi K, Amano T, Ono K, Inaba M (2006) Ubiquitylation-independent ER-associated degradation of an AE1 mutant associated with dominant hereditary spherocytosis in cattle. J Cell Sci 119:3602–3612. doi:10.1242/jcs.03101 CrossRefPubMed

Jennings ML, Gosselink PG (1995) Anion exchange protein in Southeast Asian ovalocytes: heterodimer formation between normal and variant subunits. Biochemistry 34(11):3588–3595. doi:10.1021/bi00011a013 CrossRefPubMed

Kopito RR (1990) Molecular biology of the anion exchanger gene family. Int Rev Cytol 123:177–199. doi:10.1016/S0074-7696(08)60674-9 CrossRefPubMed

Kopito RR, Lee BS, Simmons DM, Lindsey AE, Morgans CW, Schneider K (1989) Regulation of intracellular pH by a neuronal homolog of the erythrocyte anion exchanger. Cell 59(5):927–937CrossRefPubMed

Kudrycki KE, Newman PR, Shull GE (1990) cDNA cloning and tissue distribution of mRNAs for two proteins that are related to the band 3 Cl⁻/HCO₃ ⁻ exchanger. J Biol Chem 265(1):462–471PubMed

Lee CW, Rickman B, Rogers AB, Ge Z, Wang TC, Fox JG (2008) Helicobacter pylori eradication prevents progression of gastric cancer in hypergastrinemic INS-GAS mice. Cancer Res 68(9):3540–3548. doi:10.1158/0008-5472.CAN-07-6786 CrossRefPubMed

Louise MJ, Anastasia A, Carlos AR, Zachary S, Gary ES, Marian LM (2005) Gastric achlorhydria in H/K-ATPase-deficient (Atp4a(-/-)) mice causes severe hyperplasia, mucocystic metaplasia and upregulation of growth factors. J Gastroenterol Hepatol 20(8):1266–1278. doi:10.1111/j.1440-1746.2005.03867.x CrossRef

Lynch HT, Kaurah P, Wirtzfeld D, Rubinstein WS, Weissman S, Lynch JF, Grady W, Wiyrick S, Senz J, Huntsman DG (2008) Hereditary diffuse gastric cancer: diagnosis, genetic counseling, and prophylactic total gastrectomy. Cancer 112(12):2655–2663. doi:10.1002/cncr.23501 CrossRefPubMed

Meier S, Hübner CA, Groeben H, Peters J, Bingmann D, Wiemann M (2007) Expression of anion exchanger 3 influences respiratory rate in awake and isoflurane anesthetized mice. J Physiol Pharmacol 58(Suppl 5):371–378PubMed

Merchant JL (2008) What lurks beneath: IL-11, via Stat3, promotes inflammation-associated gastric tumorigenesis. J Clin Invest 118(5):1628–1631PubMed

Pang AJ, Bustos SP, Reithmeier RA (2008) Structural characterization of the cytosolic domain of kidney chloride/bicarbonate anion exchanger 1 (kAE1). Biochemistry 47(15):4510–4517. doi:10.1021/bi702149b CrossRefPubMed

Poplawski T, Tomaszewska K, Galicki M, Morawiec Z, Blasiak J (2008) Promoter methylation of cancer-related genes in gastric carcinoma. Exp Oncol 30(2):112–116PubMed

Salhany JM, Cordes KA, Schopfer LM (1993) Kinetics of conformational changes associated with inhibitor binding to the purified band 3 transporter. Direct observation of allosteric subunit interactions. Biochemistry 32(29):7413–7420. doi:10.1021/bi00080a011 CrossRefPubMed

Shen WW, Wu J, Cai L, Liu BY, Gao Y, Chen GQ, Fu GH (2007) Expression of anion exchanger 1 sequestrates p16 in the cytoplasm in gastric and colonic adenocarcinoma. Neoplasia 9(10):812–819. doi:10.1593/neo.07403 CrossRefPubMed

Sipponen P (2002) Gastric cancer: pathogenesis, risks, and prevention. J Gastroenterol 37(Suppl 13):39–44. doi:10.1007/BF02990098 CrossRefPubMed

Stewart AK, Kurschat CE, Alper SL (2007) Role of nonconserved charged residues of the AE2 transmembrane domain in regulation of anion exchange by pH. Pflugers Arch 454(3):373–384. doi:10.1007/s00424-007-0220-8 CrossRefPubMed

Sugano K (2008) Gastric cancer: pathogenesis, screening, and treatment. Gastrointest Endosc Clin N Am 18(3):513–522. doi:10.1016/j.giec.2008.05.003 CrossRefPubMed

Tanner MJ (1997) The structure and function of band 3 (AE1): recent developments. Mol Membr Biol 14(4):155–165. doi:10.3109/09687689709048178 CrossRefPubMed

Vauhkonen M, Vauhkonen H, Sajantila A, Sipponen P (2005) Differences in genomic instability between intestinal- and diffuse-type gastric cancer. Gastric Cancer 8(4):238–244. doi:10.1007/s10120-005-0346-3 CrossRefPubMed

Vauhkonen M, Vauhkonen H, Sipponen P (2006) Pathology and molecular biology of gastric cancer. Best Pract Res Clin Gastroenterol 20(4):651–674. doi:10.1016/j.bpg.2006.03.016 CrossRefPubMed

Vilkin A, Levi Z, Morgenstern S, Shmuely H, Gal E, Hadad B, Hardi B, Niv Y (2008) Higher gastric mucin secretion and lower gastric acid output in first-degree relatives of gastric cancer patients. J Clin Gastroenterol 42(1):36–41CrossRefPubMed

Yang Y, Wu PP, Wu J, Shen WW, Wu YL, Fu AF, Zheng L, Jin XL, Fu GH (2008) Expression of anion exchanger 2 in human gastric cancer. Exp Oncol 30(1):81–87PubMed

Titel: Expression of anion exchanger 1 is associated with tumor progress in human gastric cancer
verfasst von: Wei-Qing Xu
Ling-Jun Song
Qiang Liu
Lei Zhao
Lin Zheng
Zhao-Wen Yan
Guo-Hui Fu
Publikationsdatum: 01.10.2009
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0573-9

Springer Medizin

Expression of anion exchanger 1 is associated with tumor progress in human gastric cancer

Abstract

Purpose

Methods

Results

Conclusion

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 10/2009

RETRACTED ARTICLE: Overexpression of Cks1 is associated with poor survival by inhibiting apoptosis in breast cancer

APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations

Endothelin-A-receptor antagonism with atrasentan exhibits limited activity on the KU-19-19 bladder cancer cell line in a mouse model

A joint detection of CEA and CA-50 levels in saliva and serum of patients with tumors in oral region and salivary gland

Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy

Antitumor activity of the HER2 dimerization inhibitor pertuzumab on human colon cancer cells in vitro and in vivo

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie