Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Loss of Heterozygosity at the Calcium Regulation Gene Locus on Chromosome 10q in Human Pancreatic Cancer

  • Long, Jin (Department of General Surgery, the First Hospital of China Medical University) ;
  • Zhang, Zhong-Bo (Department of General Surgery, the First Hospital of China Medical University) ;
  • Liu, Zhe (Department of General Surgery, the First Hospital of China Medical University) ;
  • Xu, Yuan-Hong (Department of General Surgery, the First Hospital of China Medical University) ;
  • Ge, Chun-Lin (Department of General Surgery, the First Hospital of China Medical University)
  • Published : 2015.04.03
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. Materials and Methods: Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). Results: The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial $Ca^{2+}$ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. Conclusions: Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer.

Keywords

References

  1. Amaya K, Ohta T, Kitagawa H, et al (2004). Angiotensin II activates MAP kinase and NF-kB through angiotensin II type I receptor in human pancreatic cancer cells. Int J Oncol, 25, 849-56.
  2. Arvizo RR, Moyano DF, Saha S, et al (2013). Probing novel roles of the mitochondrial uniporter in ovarian cancer cells using nanoparticles. J Biol Chem, 288, 17610-8. https://doi.org/10.1074/jbc.M112.435206
  3. Baker DJ, Jin F, Jeganathan KB, et al (2009). Whole chromosome instability caused by Bub1 insufficiency drives tumorigenesis through tumor suppressor gene loss of heterozygosity. Cancer cell, 16, 475-86. https://doi.org/10.1016/j.ccr.2009.10.023
  4. Baughman JM, Perocchi F, Girgis HS, et al (2011). Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature, 476, 341-5. https://doi.org/10.1038/nature10234
  5. Beroukhim R, Lin M, Park Y, et al (2006). Inferring loss-of-heterozygosity from unpaired tumors using high-density oligonucleotide SNP arrays. PLoS Comput Biol, 2, 41. https://doi.org/10.1371/journal.pcbi.0020041
  6. Bick AG, Calvo SE, Mootha VK (2012). Evolutionary diversity of the mitochondrial calcium uniporter. Science, 336, 886-. https://doi.org/10.1126/science.1214977
  7. Butz J, Wickstrom E, Edwards J (2003). Characterization of mutations and loss of heterozygosity of p53 and K-ras2 in pancreatic cancer cell lines by immobilized polymerase chain reaction. BMC Biotechnol, 3, 11. https://doi.org/10.1186/1472-6750-3-11
  8. Chen K, Hsu L-T, Wu C-Y, et al (2013). CBARA1 plays a role in stemness and proliferation of human embryonic stem cells. PloS One, 8, 63653. https://doi.org/10.1371/journal.pone.0063653
  9. Contreras L, Drago I, Zampese E, et al (2010). Mitochondria: the calcium connection. BBA-Gen Subjects, 1797, 607-18.
  10. Csordas G, Golenar T, Seifert EL, et al (2013). MICU1 controls both the threshold and cooperative activation of the mitochondrial $Ca^{2+}$ uniporter. Cell Metab, 17, 976-87. https://doi.org/10.1016/j.cmet.2013.04.020
  11. Csordas G, Varnai P, Golenar T, et al (2012). Calcium transport across the inner mitochondrial membrane: molecular mechanisms and pharmacology. Mol Cell Endocrinol, 353, 109-13. https://doi.org/10.1016/j.mce.2011.11.011
  12. Curry MC, Peters AA, Kenny PA, et al (2013). Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells. Biochem Biophys Res Commun, 434, 695-700. https://doi.org/10.1016/j.bbrc.2013.04.015
  13. Day IN (2010). dbSNP in the detail and copy number complexities. Hum Mutat, 31, 2-4. https://doi.org/10.1002/humu.21149
  14. Donahue TR, Tran LM, Hill R, et al (2012). Integrative survival-based molecular profiling of human pancreatic cancer. Clin Cancer Res, 18, 1352-63. https://doi.org/10.1158/1078-0432.CCR-11-1539
  15. Elnemr A, Ohta T, Iwata K, et al (2000). PPARgamma ligand (thiazolidinedione) induces growth arrest and differentiation markers of human pancreatic cancer cells. Int J Oncol, 17, 1157-221.
  16. Frampton SJ, King EV (2013). Loss of heterozygosity. in 'encyclopedia of otolaryngology, head and neck surgery', Eds Springer, 1488
  17. Franko J, Krasinskas AM, Nikiforova MN, et al (2008). Loss of heterozygosity predicts poor survival after resection of pancreatic adenocarcinoma. J Gastrointest Surg, 12, 1664-73. https://doi.org/10.1007/s11605-008-0577-9
  18. Fujita PA, Rhead B, Zweig AS, et al (2010). The UCSC genome browser database: update 2011. Nucleic Acids Res, 963.
  19. Hoffman NE, Chandramoorthy HC, Shamugapriya S, et al (2013). MICU1 motifs define mitochondrial calcium uniporter binding and activity. Plant Cell Rep, 5, 1576-88. https://doi.org/10.1016/j.celrep.2013.11.026
  20. Kohl M, Wiese S, Warscheid B (2011). Cytoscape: software for visualization and analysis of biological networks. , Eds Springer, 696, 291-303 https://doi.org/10.1007/978-1-60761-987-1_18
  21. Kopp JL, von Figura G, Mayes E, et al (2012). Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell, 22, 737-50. https://doi.org/10.1016/j.ccr.2012.10.025
  22. Kroemer G, Galluzzi L, Brenner C (2007). Mitochondrial membrane permeabilization in cell death. Physiol Rev, 87, 99-163. https://doi.org/10.1152/physrev.00013.2006
  23. Lin L-J, Asaoka Y, Tada M, et al (2008). Integrated analysis of copy number alterations and loss of heterozygosity in human pancreatic cancer using a high-resolution, single nucleotide polymorphism array. Oncol, 75, 102-12. https://doi.org/10.1159/000155813
  24. Logan CV, Szabadkai G, Sharpe JA, et al (2014). Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling. Nat Genet, 46, 188-93.
  25. Lucas AL, Shakya R, Lipsyc MD, et al (2013). High prevalence of BRCA1 and BRCA2 germline mutations with loss of heterozygosity in a series of resected pancreatic adenocarcinoma and other neoplastic lesions. Clin Cancer Res, 19, 3396-403. https://doi.org/10.1158/1078-0432.CCR-12-3020
  26. Mallilankaraman K, Doonan P, Cardenas C, et al (2012). MICU1 Is an essential gatekeeper for MCU-mediated mitochondrial Ca< sup>2+ uptake that regulates cell survival. Cell, 151, 630-44. https://doi.org/10.1016/j.cell.2012.10.011
  27. Marchi S, Lupini L, Patergnani S, et al (2013). Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25. Curr Biol, 23, 58-63.
  28. Morton JP, Timpson P, Karim SA, et al (2010). Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci, 107, 246-51. https://doi.org/10.1073/pnas.0908428107
  29. Patron M, Raffaello A, Granatiero V, et al (2013). The mitochondrial calcium uniporter (MCU): molecular identity and physiological roles. J Biol Chem, 288, 10750-8. https://doi.org/10.1074/jbc.R112.420752
  30. Perocchi F, Gohil VM, Girgis HS, et al (2010). MICU1 encodes a mitochondrial EF hand protein required for $Ca^{2+}$ uptake. Nature, 467, 291-6. https://doi.org/10.1038/nature09358
  31. Raffaello A, De Stefani D, Rizzuto R (2012). The mitochondrial $Ca^{2+}$ uniporter. Cell Calcium, 52, 16-21. https://doi.org/10.1016/j.ceca.2012.04.006
  32. Sahu RP, Srivastava SK (2009). The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate. J Natl Cancer Inst, 101, 176-93. https://doi.org/10.1093/jnci/djn470
  33. Sato Y, Nio Y, Song M, et al (1996). p53 protein expression as prognostic factor in human pancreatic cancer. Anticancer Res, 17, 2779-88.
  34. Scorrano L, Oakes SA, Opferman JT, et al (2003). BAX and BAK regulation of endoplasmic reticulum $Ca^{2+}$: a control point for apoptosis. Science, 300, 135-9. https://doi.org/10.1126/science.1081208
  35. Sherman BT, Huang dW, Tan Q, et al (2007). DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinformatics, 8, 426. https://doi.org/10.1186/1471-2105-8-426
  36. Staaf J, Lindgren D, Vallon-Christersson J, et al (2008). Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays. Genome Biol, 9, 136. https://doi.org/10.1186/gb-2008-9-9-r136
  37. Xu ZG, Du JJ, Zhang X, et al (2003). A novel liver-specific zona pellucida domain containing protein that is expressed rarely in hepatocellular carcinoma. Hepatology, 38, 735-44.
  38. Yoshida T, Kobayashi T, Itoda M, et al (2010). Clinical omics analysis of colorectal cancer incorporating copy number aberrations and gene expression data. Cancer Informatics, 9, 147.
  39. Zhang Y, Bharadwaj U, Logsdon CD, et al (2010). ZIP4 regulates pancreatic cancer cell growth by activating IL-6/STAT3 pathway through zinc finger transcription factor CREB. Clin Cancer Res, 16, 1423-30. https://doi.org/10.1158/1078-0432.CCR-09-2405

Cited by

  1. Expression and influence of Notch signaling in oral squamous cell carcinoma vol.58, pp.2, 2016, https://doi.org/10.2334/josnusd.15-0535
  2. Structure, Activity Regulation, and Role of the Mitochondrial Calcium Uniporter in Health and Disease vol.7, pp.2234-943X, 2017, https://doi.org/10.3389/fonc.2017.00139
  3. Voltage-gated calcium channels: Novel targets for cancer therapy vol.14, pp.2, 2017, https://doi.org/10.3892/ol.2017.6457