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Alteration in methylation pattern of oncogene Akt1 promoter region in bladder cancer

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Abstract

The oncogene Akt1 plays a pivotal role in regulating growth factor-associated cell survival. The activity of Akt must be carefully regulated as it has been reported that an increase in Akt signaling is frequently associated with cancer. Phosphorylated Akt, as the constitutively activated form of Akt, has been observed in many kinds of cancer, but the clinical relevance of the (DNA) methylation profile of Akt1 in cancer is not well understood. This study aims to investigate the methylation level of Akt1 in bladder cancer tissues and their clinical significance. Methylation of the oncogene Akt1 transcriptional regulation region (TRR) was detected using bisulfite-specific (BSP) PCR-based sequencing analysis in cases of bladder cancer and the normal tissues, including 15 bladder cancer tissues, and five normal bladder tissues. BSP cloning-based sequencing analysis was also performed in selected cases. Clinicopathological data from the cancer patients were collected and analyzed. Analysis of Akt1 gene TRR methylation showed decreased methylation level in bladder cancer than normal. Methylation level of Akt1 has clinical relevance (P = 0.0043 by unpaired student’s t test) with bladder cancer. Abnormal methylation of the Akt1 gene may be an early event during urocystic tumorigenesis and should be further evaluated as a tumorigenesis marker for early detection of bladder cancer.

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References

  1. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501

    Article  PubMed  CAS  Google Scholar 

  2. Ermoian RP, Furniss CS, Lamborn KR et al (2002) Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival. Clin Cancer Res 8:1100–1106

    PubMed  CAS  Google Scholar 

  3. Ruggeri BA, Huang L, Wood M et al (1998) Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol Carcinog 21:81–86

    Article  PubMed  CAS  Google Scholar 

  4. Malik SN, Brattain M, Ghosh PM et al (2002) Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer. Clin Cancer Res 8:1168–1171

    PubMed  Google Scholar 

  5. Carpten JD, Faber AL, Horn C et al (2007) A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448(7152):439–444

    Article  PubMed  CAS  Google Scholar 

  6. Do H, Solomon B, Mitchell PL et al (2008) Detection of the transforming AKT1 mutation E17K in non-small cell lung cancer by high resolution melting. BMC Res Notes 1:14

    Article  PubMed  Google Scholar 

  7. Askham JM, Platt F, Chambers PA et al (2010) AKT1 mutations in bladder cancer: identification of a novel oncogenic mutation that can co-operate with E17K. Oncogene 29(1):150–155

    Article  PubMed  CAS  Google Scholar 

  8. Chung JY, Hong SM, Choi BY et al (2009) The expression of phospho-AKT, phospho-mTOR, and PTEN in extrahepatic cholangiocarcinoma. Clin Cancer Res 15(2):660–667

    Article  PubMed  CAS  Google Scholar 

  9. Chang X, Ravi R, Pham V et al (2011) Adenylate kinase 3 sensitizes cells to cigarette smoke condensate vapor induced cisplati n resistance. PLoS One 6(6):e20806

    Article  PubMed  CAS  Google Scholar 

  10. Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349(21):2042–2054

    Article  PubMed  CAS  Google Scholar 

  11. Pan B, Chao H, Chen B et al (2011) DNA methylation of germ cell-specific basic helix-loop-helix (HLH) transcription factors, Sohlh2 and Figlα during gametogenesis. Mol Hum Reprod 17(9):550–561

    Article  PubMed  CAS  Google Scholar 

  12. Bird AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321:209–213

    Article  PubMed  CAS  Google Scholar 

  13. Adrien LR, Schlecht NF, Kawachi N et al (2006) Classification of DNA methylation patterns in tumor cell genomes using a CpG island microarray. Cytogenet Genome Res 114:16–23

    Article  PubMed  CAS  Google Scholar 

  14. Sato N, Goggins M (2006) Epigenetic alterations in intraductal papillary mucinous neoplasms of the pancreas. J Hepatobiliary Pancreat Surg 13:280–285

    Article  PubMed  Google Scholar 

  15. Torng PL, Lin CW, Chan MW et al (2009) Promoter methylation of IGFBP-3 and p53 expression in ovarian endometrioid carcinoma. Mol Cancer 8:120

    Article  PubMed  Google Scholar 

  16. Watts GS, Futscher BW, Holtan N et al (2008) DNA methylation changes in ovarian cancer are cumulative with disease progression and identify tumor stage. BMC Med Genomics 1:47

    Article  PubMed  Google Scholar 

  17. Aleman A, Adrien L, Lopez-Serra L et al (2008) Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays. Br J Cancer 98(2):466–473

    Article  PubMed  CAS  Google Scholar 

  18. Du P, Ye HR, Gao J et al (2009) Methylation of PTCH1a gene in a subset of gastric cancers. World J Gastroenterol 15(30):3799–3806

    Article  PubMed  CAS  Google Scholar 

  19. Gao J, Song J, Huang H et al (2010) Methylation of the SPARC gene promoter and its clinical implication in pancreatic cancer. J Exp Clin Cancer Res 29:28

    Article  PubMed  CAS  Google Scholar 

  20. Shargh SA, Sakizli M, Farajnia S et al (2011) Evaluation of methylation pattern in promoter region of E-cadherin gene and its relation to tumor grade and stage in breast cancer. Afr J Biotechnol 10(10):1745–1751

    CAS  Google Scholar 

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Acknowledgments

This work was supported by National Nature Science Foundation (31001010 and 31101716), Foundation of Distinguished Young Scholars (JQ201109), Doctoral Foundation (BS2010NY010), Foundation of Education Department (J11LC20) and Taishan Scholar Foundation of Shandong Province, and Doctoral Foundation (630917) of Qingdao Agricultural University.

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Correspondence to Wei Shen.

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Xiao-Feng Sun and Zhong-Yi Sun both are co-first authors.

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Sun, XF., Sun, ZY., Pan, B. et al. Alteration in methylation pattern of oncogene Akt1 promoter region in bladder cancer. Mol Biol Rep 39, 5631–5636 (2012). https://doi.org/10.1007/s11033-011-1369-y

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  • DOI: https://doi.org/10.1007/s11033-011-1369-y

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