Copy-number Increase of AURKA in Gastric Cancers in a Chinese Population: a Correlation with Tumor Progression

Overview

Journal Med Oncol

Publisher Springer

Specialty Oncology

Date 2010 Jun 30

PMID 20585902

Citations 7

Authors

Zhengyu Fang

Yi Xiong

Jiana Li

Li Liu

Manhui Li

Chao Zhang

Wei Zhang

Jun Wan

Affiliations

Soon will be listed here.

Abstract

The centrosome-associated kinase aurora A (AURKA) has been shown to be involved in genetic instability and to be over-expressed in several human carcinomas including gastric cancers (GCs). The chromosome locus of AURKA, 20q13, is frequently amplified in GCs, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of gastric carcinomas and adjacent normal epithelium (n=141) were included in this study. Quantitative PCR was carried out to examine the copy number and mRNA expression of AURKA in GCs. Our results showed copy-number gains of AUKRA were detected in a relative high percentage of GC samples (30.5%, 43 out of 141). There was a positive correlation between copy-number increase of AURKA and tumor progression. And copy-number gains of AURKA also showed a positive correlation with mRNA over-expression in GCs. However, expression level of AURKA mRNA was also enhanced in the group of GC samples with unaltered copy numbers. These findings indicated that sporadic gastric cancers exhibit different mechanisms of AURKA regulation and that this may impact the efficacy of aurora-targeted therapies.

Citing Articles

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Recombinant human bone morphogenetic protein-2 inhibits gastric cancer cell proliferation by inactivating Wnt signaling pathway via c-Myc with aurora kinases.

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References

Vauhkonen H, Vauhkonen M, Sipponen P, Knuutila S . Oligonucleotide array comparative genomic hybridization refines the structure of 8p23.1, 17q12 and 20q13.2 amplifications in gastric carcinomas. Cytogenet Genome Res. 2007; 119(1-2):39-45. DOI: 10.1159/000109617. View

Dar A, Zaika A, Piazuelo M, Correa P, Koyama T, Belkhiri A . Frequent overexpression of Aurora Kinase A in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions. Cancer. 2008; 112(8):1688-98. PMC: 4030394. DOI: 10.1002/cncr.23371. View

Sakakura C, Hagiwara A, Yasuoka R, Fujita Y, Nakanishi M, Masuda K . Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. Br J Cancer. 2001; 84(6):824-31. PMC: 2363814. DOI: 10.1054/bjoc.2000.1684. View

Jeng Y, Peng S, Lin C, Hsu H . Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Res. 2004; 10(6):2065-71. DOI: 10.1158/1078-0432.ccr-1057-03. View

Kyrlagkitsis I, Karamanolis D . Genes and gastric cancer. Hepatogastroenterology. 2004; 51(55):320-7. View

Guryev V, Saar K, Adamovic T, Verheul M, van Heesch S, Cook S . Distribution and functional impact of DNA copy number variation in the rat. Nat Genet. 2008; 40(5):538-45. DOI: 10.1038/ng.141. View

Reymond A, Henrichsen C, Harewood L, Merla G . Side effects of genome structural changes. Curr Opin Genet Dev. 2007; 17(5):381-6. DOI: 10.1016/j.gde.2007.08.009. View

Wu C, Chi C, Lin W . Gastric cancer: prognostic and diagnostic advances. Expert Rev Mol Med. 2004; 4(6):1-12. DOI: 10.1017/S1462399402004337. View

Goepfert T, Brinkley B . The centrosome-associated Aurora/Ipl-like kinase family. Curr Top Dev Biol. 2000; 49:331-42. DOI: 10.1016/s0070-2153(99)49016-7. View

10.

Andrews J, Kennette W, Pilon J, Hodgson A, Tuck A, Chambers A . Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number. PLoS One. 2010; 5(1):e8665. PMC: 2801616. DOI: 10.1371/journal.pone.0008665. View

11.

Grubor V, Krasnitz A, Troge J, Meth J, Lakshmi B, Kendall J . Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA). Blood. 2008; 113(6):1294-303. DOI: 10.1182/blood-2008-05-158865. View

12.

Vauhkonen H, Vauhkonen M, Sajantila A, Sipponen P, Knuutila S . DNA copy number aberrations in intestinal-type gastric cancer revealed by array-based comparative genomic hybridization. Cancer Genet Cytogenet. 2006; 167(2):150-4. DOI: 10.1016/j.cancergencyto.2005.11.014. View

13.

Dear P . Copy-number variation: the end of the human genome?. Trends Biotechnol. 2009; 27(8):448-54. DOI: 10.1016/j.tibtech.2009.05.003. View

14.

Diskin S, Hou C, Glessner J, Attiyeh E, Laudenslager M, Bosse K . Copy number variation at 1q21.1 associated with neuroblastoma. Nature. 2009; 459(7249):987-91. PMC: 2755253. DOI: 10.1038/nature08035. View

15.

Li D, Zhu J, Firozi P, Abbruzzese J, Evans D, Cleary K . Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin Cancer Res. 2003; 9(3):991-7. View

16.

Park H, Park W, Bondaruk J, Tanaka N, Katayama H, Lee S . Quantitation of Aurora kinase A gene copy number in urine sediments and bladder cancer detection. J Natl Cancer Inst. 2008; 100(19):1401-11. PMC: 2720731. DOI: 10.1093/jnci/djn304. View

17.

Nishida N, Nagasaka T, Kashiwagi K, Boland C, Goel A . High copy amplification of the Aurora-A gene is associated with chromosomal instability phenotype in human colorectal cancers. Cancer Biol Ther. 2007; 6(4):525-33. DOI: 10.4161/cbt.6.4.3817. View

18.

Tanaka E, Hashimoto Y, Ito T, Okumura T, Kan T, Watanabe G . The clinical significance of Aurora-A/STK15/BTAK expression in human esophageal squamous cell carcinoma. Clin Cancer Res. 2005; 11(5):1827-34. DOI: 10.1158/1078-0432.CCR-04-1627. View

19.

Kamada K, Yamada Y, Hirao T, Fujimoto H, Takahama Y, Ueno M . Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis. Oncol Rep. 2004; 12(3):593-9. View

20.

Agnese V, Cabibi D, Calcara D, Terrasi M, Pantuso G, Fiorentino E . Aurora-A overexpression as an early marker of reflux-related columnar mucosa and Barrett's oesophagus. Ann Oncol. 2007; 18 Suppl 6:vi110-5. DOI: 10.1093/annonc/mdm237. View