DOI QR코드

DOI QR Code

Expression Profile and Potential Roles of EVA1A in Normal and Neoplastic Pancreatic Tissues

  • Tao, Ming (Department of General Surgery, Peking University Third Hospital) ;
  • Shi, Xue-Ying (Department of Pathology, Ministry of Health, Peking University Health Science Center) ;
  • Yuan, Chun-Hui (Department of General Surgery, Peking University Third Hospital) ;
  • Hu, Jia (Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center) ;
  • Ma, Zhao-Lai (Department of General Surgery, Peking University Third Hospital) ;
  • Jiang, Bin (Department of General Surgery, Peking University Third Hospital) ;
  • Xiu, Dian-Rong (Department of General Surgery, Peking University Third Hospital) ;
  • Chen, Ying-Yu (Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center)
  • Published : 2015.02.04

Abstract

Background: EVA1A (eva-1 homolog A) is a novel gene that regulates programmed cell death through autophagy and apoptosis. Our objective was to investigate the expression profiles and potential role of EVA1A in normal and neoplastic human pancreatic tissues. Materials and Methods: The expression pattern of EVA1A in normal pancreatic tissue was examined by indirect immunofluorescence and confocal microscopy. Protein levels in paraffin-embedded specimens from normal and diseased pancreatic and matched non-tumor tissues were evaluated by immunohistochemistry. Results: EVA1A colocalized with glucagon but not with insulin, demonstrating production in islet alpha cells. Itwas strongly expressed in chronic pancreatitis, moderately or weakly expressed in the plasma membrane and cytoplasm in pancreatic acinar cell carcinoma, and absent in normal pancreatic acinar cells. Although the tissue architecture was deformed, EVA1A was absent in the alpha cells of pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms, mucinous cystadenomas, solid papillary tumors and pancreatic neuroendocrine tumors. Conclusions: EVA1A protein is specifically expressed in islet alpha cells, suggesting it may play an important role in regulating alpha-cell function. The ectopic expression of EVA1A in pancreatic neoplasms may contribute to their pathogenesis and warrants further investigation.

Keywords

References

  1. Armstrong MD, Von Hoff D, Barber B, et al (2011). An effective personalized approach to a rare tumor: prolonged survival in metastatic pancreatic acinar cell carcinoma based on genetic analysis and cell line development. J Cancer, 2, 142-52.
  2. Chang Y, Li Y, Hu J, et al (2013). Adenovirus vector-mediated expression of TMEM166 inhibits human cancer cell growth by autophagy and apoptosis in vitro and in vivo. Cancer Lett, 328, 126-34. https://doi.org/10.1016/j.canlet.2012.08.032
  3. Donath MY (2013). Targeting inflammation in the treatment of type 2 diabetes. Diabetes Obes Metab, 15, 193-6.
  4. Jung HS, Chung KW, Won KJ, et al (2008). Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab, 8, 318-24. https://doi.org/10.1016/j.cmet.2008.08.013
  5. Kuo EJ, Salem RR (2013). Population-level analysis of pancreatic neuroendocrine tumors 2 cm or less in size. Ann Surg Oncol, 20, 2815-21. https://doi.org/10.1245/s10434-013-3005-7
  6. La Rosa S, Adsay V, Albarello L, et al (2012). Clinicopathologic study of 62 acinar cell carcinomas of the pancreas: insights into the morphology and immunophenotype and search for prognostic markers. Am J Surg Pathol, 36, 1782-95. https://doi.org/10.1097/PAS.0b013e318263209d
  7. Li L, Khatibi NH, Hu Q, et al (2012). Transmembrane protein 166 regulates autophagic and apoptotic activities following focal cerebral ischemic injury in rats. Exp Neurol, 234, 181-90. https://doi.org/10.1016/j.expneurol.2011.12.038
  8. Poruk KE, Firpo MA, Adler DG, et al (2013). Screening for pancreatic cancer: why, how, and who? Ann Surg, 257, 17-26. https://doi.org/10.1097/SLA.0b013e31825ffbfb
  9. Quan W, Jo EK, Lee MS (2013). Role of pancreatic beta-cell death and inflammation in diabetes. Diabetes Obes Metab, 15, 141-51 https://doi.org/10.1111/dom.12153
  10. Rivera JF, Gurlo T, Daval M, et al (2011). Human-IAPP disrupts the autophagy/lysosomal pathway in pancreatic $\beta$-cells: protective role of p62-positive cytoplasmic inclusions. Cell Death Differ, 18, 415-26. https://doi.org/10.1038/cdd.2010.111
  11. Rivera JF, Costes S, Gurlo T, et al (2014). Autophagy defends pancreatic $\beta$ cells from human islet amyloid polypeptideinduced toxicity. J Clin Invest, 124, 3489-500. https://doi.org/10.1172/JCI71981
  12. Sumiyoshi T, Shima Y, Okabayashi T, et al (2013). Comparison of pancreatic acinar cell carcinoma and adenocarcinoma using multidetector-row computed tomography. World J Gastroenterol, 19, 5713-9. https://doi.org/10.3748/wjg.v19.i34.5713
  13. Sun W, Ma XM, Bai JP, et al (2012). Transmembrane protein 166 expression in esophageal squamous cell carcinoma in xinjiang, China. Asian Pac J Cancer Prev, 13, 3713-6. https://doi.org/10.7314/APJCP.2012.13.8.3713
  14. Wang L, Yu C, Lu Y, et al (2007). TMEM166, a novel transmembrane protein, regulates cell autophagy and apoptosis. Apoptosis, 12, 1489-502. https://doi.org/10.1007/s10495-007-0073-9
  15. Wilcox CL, Terry NA, May CL (2013). Arx polyalanine expansion in mice leads to reduced pancreatic alpha-cell specification and increased alpha-cell death. PLoS One, 8, 78741. https://doi.org/10.1371/journal.pone.0078741
  16. Wu Y, Wu T, Wu J, et al (2013). Chronic inflammation exacerbates glucose metabolism disorders in C57BL/6J mice fed with high-fat diet. J Endocrinol, 219, 195-204. https://doi.org/10.1530/JOE-13-0160
  17. Xie H, Hu J, Pan H, et al (2014). Adenovirus vector-mediated FAM176A overexpression induces cell death in human H1299 non-small cell lung cancer cells. BMB Rep, 47, 104-9. https://doi.org/10.5483/BMBRep.2014.47.2.090
  18. Xu D, Yang F, He H, et al (2013). Expression of TMEM166 protein in human normal and tumor tissues. Appl Immunohistochem Mol Morphol, 21, 543-52. https://doi.org/10.1097/PAI.0b013e31824e93d1