期刊论文详细信息
BMC Gastroenterology
Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure
Anson W Lowe1  M Bishr Omary2  Peyman Sahbaie2  Zheng Wang3  Jong Hyeok Kim3  George Triadafilopoulos3  Sumita Sood3  Ying Hao3 
[1]Stanford University Digestive Disease Center, Stanford, CA, USA
[2]Gastroenterology Section, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA
[3]Department of Medicine, Stanford University, Stanford, CA, USA
Others  :  1211647
DOI  :  10.1186/1471-230X-7-24
 received in 2007-01-19, accepted in 2007-06-27,  发布年份 2007
PDF
【 摘 要 】

Background

Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation.

Methods

Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment.

Results

The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure.

Conclusion

Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus in vivo.

【 授权许可】

   
2007 Hao et al; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150610020442295.pdf 712KB PDF download
Figure 4. 107KB Image download
Figure 3. 242KB Image download
Figure 2. 261KB Image download
Figure 1. 79KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Brown LM, Devesa SS: Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am 2002, 11(2):235-256.
  • [2]Paulson TG, Reid BJ: Focus on Barrett's esophagus and esophageal adenocarcinoma. Cancer Cell 2004, 6(1):11-16.
  • [3]Lagergren J, Bergstrom R, Lindgren A, Nyren O: Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999, 340(11):825-831.
  • [4]Hao Y, Triadafilopoulos G, Sahbaie P, Young HS, Omary MB, Lowe AW: Gene expression profiling reveals stromal genes expressed in common between Barrett's esophagus and adenocarcinoma. Gastroenterology 2006, 131(3):925-933.
  • [5]Souza RF, Shewmake K, Terada LS, Spechler SJ: Acid exposure activates the mitogen-activated protein kinase pathways in Barrett's esophagus. Gastroenterology 2002, 122(2):299-307.
  • [6]Souza RF, Shewmake K, Pearson S, Sarosi GA Jr, Feagins LA, Ramirez RD, Terada LS, Spechler SJ: Acid increases proliferation via ERK and p38 MAPK-mediated increases in cyclooxygenase-2 in Barrett's adenocarcinoma cells. Am J Physiol Gastrointest Liver Physiol 2004, 287(4):G743-748.
  • [7]Sarosi GA Jr, Jaiswal K, Herndon E, Lopez-Guzman C, Spechler SJ, Souza RF: Acid increases MAPK-mediated proliferation in Barrett's esophageal adenocarcinoma cells via intracellular acidification through a Cl-/HCO3- exchanger. Am J Physiol Gastrointest Liver Physiol 2005, 289(6):G991-997.
  • [8]Fitzgerald RC, Omary MB, Triadafilopoulos G: Dynamic effects of acid on Barrett's esophagus. An ex vivo proliferation and differentiation model. J Clin Invest 1996, 98(9):2120-2128.
  • [9]Kaur BS, Ouatu-Lascar R, Omary MB, Triadafilopoulos G: Bile salts induce or blunt cell proliferation in Barrett's esophagus in an acid-dependent fashion. Am J Physiol Gastrointest Liver Physiol 2000, 278(6):G1000-1009.
  • [10]Shirvani VN, Ouatu-Lascar R, Kaur BS, Omary MB, Triadafilopoulos G: Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure. Gastroenterology 2000, 118(3):487-496.
  • [11]Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al.: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001, 98(19):10869-10874.
  • [12]Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, et al.: Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA 2004, 101(3):811-816.
  • [13]Soldes OS, Kuick RD, Thompson IA 2nd, Hughes SJ, Orringer MB, Iannettoni MD, Hanash SM, Beer DG: Differential expression of Hsp27 in normal oesophagus, Barrett's metaplasia and oesophageal adenocarcinomas. Br J Cancer 1999, 79(3–4):595-603.
  • [14]Rockett JC, Larkin K, Darnton SJ, Morris AG, Matthews HR: Five newly established oesophageal carcinoma cell lines: phenotypic and immunological characterization. Br J Cancer 1997, 75(2):258-263.
  • [15]Nishihira T, Hashimoto Y, Katayama M, Mori S, Kuroki T: Molecular and cellular features of esophageal cancer cells. J Cancer Res Clin Oncol 1993, 119(8):441-449.
  • [16]Patrick Brown's laboratory protocols, Stanford University [http://cmgm.stanford.edu/pbrown/protocols/index.html] webcite
  • [17]Alizadeh AA, Eisen MB, Davis RE, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, et al.: Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000, 403:503-511.
  • [18]Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al.: Molecular portraits of human breast tumours. Nature 2000, 406(6797):747-752.
  • [19]Stanford functional genomics facility [http://www.microarray.org/sfgf/] webcite
  • [20]Stanford Microarray Database [http://genome-www5.stanford.edu/] webcite
  • [21]Sherlock G, Hernandez-Boussard T, Kasarskis A, Binkley G, Matese JC, Dwight SS, Kaloper M, Weng S, Jin H, Ball CA, et al.: The Stanford Microarray Database. Nucleic Acids Res 2001, 29(1):152-155.
  • [22]Eisen MB, Spellman PT, Brown PO, Botstein D: Cluster analysis and display of genome-wide expression patterns. ProcNatlAcadSciUSA 1998, 95(25):14863-14868.
  • [23]Tusher VG, Tibshirani R, Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 2001, 98(9):5116-5121.
  • [24]Zeeberg BR, Feng W, Wang G, Wang MD, Fojo AT, Sunshine M, Narasimhan S, Kane DW, Reinhold WC, Lababidi S, et al.: GoMiner: a resource for biological interpretation of genomic and proteomic data. Genome Biol 2003, 4(4):R28. BioMed Central Full Text
  • [25]Zeeberg BR, Qin H, Narasimhan S, Sunshine M, Cao H, Kane DW, Reimers M, Stephens RM, Bryant D, Burt SK, et al.: High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of Common Variable Immune Deficiency (CVID). BMC Bioinformatics 2005, 6:168. BioMed Central Full Text
  • [26]Anson Lowe's laboratory website
  • [27]van de Loosdrecht AA, Beelen RH, Ossenkoppele GJ, Broekhoven MG, Langenhuijsen MM: A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia. J Immunol Methods 1994, 174(1–2):311-320.
  • [28]Towbin H, Staehelin T, Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. ProcNatlAcadSciUSA 1979, 76(9):4350-4354.
  • [29]Batteiger B, Newhall WJ, Jones RB: The use of tween 20 as a blocking agent in the immunological detection of proteins transferred to nitrocellulose membranes. JImmunolMethods 1982, 55(3):297-307.
  • [30]Jaiswal K, Lopez-Guzman C, Souza RF, Spechler SJ, Sarosi GA Jr: Bile salt exposure increases proliferation through p38 and ERK MAPK pathways in a non-neoplastic Barrett's cell line. Am J Physiol Gastrointest Liver Physiol 2006, 290(2):G335-342.
  • [31]Morgan C, Alazawi W, Sirieix P, Freeman T, Coleman N, Fitzgerald R: In vitro acid exposure has a differential effect on apoptotic and proliferative pathways in a Barrett's adenocarcinoma cell line. Am J Gastroenterol 2004, 99(2):218-224.
  • [32]Harris MA, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R, Eilbeck K, Lewis S, Marshall B, Mungall C, et al.: The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res 2004, (32 Database):D258-261.
  • [33]Palanca-Wessels MC, Barrett MT, Galipeau PC, Rohrer KL, Reid BJ, Rabinovitch PS: Genetic analysis of long-term Barrett's esophagus epithelial cultures exhibiting cytogenetic and ploidy abnormalities. Gastroenterology 1998, 114(2):295-304.
  • [34]Palanca-Wessels MC, Klingelhutz A, Reid BJ, Norwood TH, Opheim KE, Paulson TG, Feng Z, Rabinovitch PS: Extended lifespan of Barrett's esophagus epithelium transduced with the human telomerase catalytic subunit: a useful in vitro model. Carcinogenesis 2003, 24(7):1183-1190.
  文献评价指标  
  下载次数:41次 浏览次数:8次