Skip to main content
Log in

A-Kinase Anchoring Proteins 10 Expression in Relation to 2073A/G Polymorphism and Tumor Progression in Patients with Colorectal Cancer

  • Research
  • Published:
Pathology & Oncology Research

Abstract

The cAMP/PKA signalling events regulated by A-kinase anchoring proteins 10 (AKAP10) is involved in tumorigenesis. Previous study showed that AKAP10 polymorphism (2073 A/G, I646V) was associated with colorectal cancer risk. However, there was no literature reporting the role of AKAP10 in the pathogenesis of colorectal cancer. The aim of the study was to investigate the clinicopathologic significance of A-kinase anchoring proteins 10 (AKAP 10) expression and the relationship with its polymorphism in colorectal cancer. The expression of AKAP10 was determined by immunohistochemical staining (IHC) and western blot assay on colorectal cancer (n = 176), adenoma (n = 87) and distant normal mucosa (n = 72). 176 patients with colorectal cancer were genotyped for AKAP10 2073A/G polymorphism by TaqMan RT-PCR. We found that the positive expression rate of AKAP10 in colorectal cancer (59 %) was significantly higher than those in adenoma (39 %) and distant normal mucosa (42 %) (P = 0.004). There was no significant difference between adenoma and distant normal mucosa (P = 0.741). Positive AKAP10 staining was correlated with deeper tumor invasion (P < 0.001), lymph nodes metastasis (P = 0.022), advanced tumor stage (P < 0.001) and poorly differentiated degree (P = 0.003). Compared with AA genotype (52 %), positive expression of AKAP10 was significantly increased in colorectal cancer patients with the variant (AG+GG) genotypes (68 %, P = 0.033). It was concluded that AKAP10 may play an important role in the development and progression of colorectal cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Vogelstein B, Fearon ER, Hamilton SR et al (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532

    Article  PubMed  CAS  Google Scholar 

  2. Cho YS, Park YG, Lee YN et al (2000) Extracellular protein kinase A as a cancer biomarker: its expression by tumor cells and reversal by a myristatelacking Ca and RIIβ subunit overexpression. Proc Natl Acad Sci USA 97:835–840

    Article  PubMed  CAS  Google Scholar 

  3. Wong W, Scott JD (2004) AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol 5:959–970

    Article  PubMed  CAS  Google Scholar 

  4. Huang L, Durick K, Weiner JA, Chun J, Taylor SS (1997) D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain. Proc Natl Acad Sci USA 94:11184–11189

    Article  PubMed  CAS  Google Scholar 

  5. Hamuro Y, Burns L, Canaves J, Hoffman R, Taylor SS, Woods V (2002) Domain organization of D-AKAP2 revealed by enhanced deuterium exchange-mass spectrometry (DXMS). J Mol Biol 321:703–714

    Article  PubMed  CAS  Google Scholar 

  6. Sheng M, Sala C (2001) PDZ domains and the organization of supramolecular complexes. Annu Rev Neurosci 24:1–29

    Article  PubMed  CAS  Google Scholar 

  7. Wang L, Sunahara RK, Krumins A et al (2001) Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein. Proc Natl Acad Sci USA 98:3220–3225

    Article  PubMed  CAS  Google Scholar 

  8. Burns-Hamuro LL, Barraclough DM, Taylor SS (2004) Identification and functional analysis of dual-specific A kinase-anchoring protein-2. Methods Enzymol 390:354–374

    Article  PubMed  CAS  Google Scholar 

  9. Neary CL, Nesterova M, Cho YS, Cheadle C, Becker KG, Cho-Chung YS (2004) Protein kinase A isozyme switching: eliciting differential cAMP signaling and tumor reversion. Oncogene 23:8847–8856

    Article  PubMed  CAS  Google Scholar 

  10. Cross TG, Scheel-Toellner D, Henriquez NV, Deacon E, Salmon M, Lord JM (2000) Serine/threonine protein kinases and apoptosis. Exp Cell Res 256:34–41

    Article  PubMed  CAS  Google Scholar 

  11. Tasken K, Skalhegg BS, Tasken KA et al (1997) Structure, function, and regulation of human cAMP-dependent protein kinases. Adv Second Messenger Phosphoprotein Res 31:191–204

    Article  PubMed  CAS  Google Scholar 

  12. Wirtenberger M, Schmutzhard J, Hemminkil K et al (2007) The functional genetic variant Ile646Val located in the kinase binding domain of the A-kinase anchoring protein 10 is associated with familial breast cancer. Carcinogenesis 28:423–426

    Article  PubMed  CAS  Google Scholar 

  13. Wang MJ, Zhou ZG, Wang L et al (2009) The Ile646Val (2073A>G) Polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 and the risk of colorectal cancer. Oncology 76:199–204

    Article  PubMed  CAS  Google Scholar 

  14. Compton CC, Greene FL (2004) The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin 54:295–308

    Article  PubMed  Google Scholar 

  15. Yang L, Zhang H, Zhou ZG, Yan H, Adell G, Sun XF (2011) Biological function and prognostic significance of peroxisome proliferator-activated receptor δ in rectal cancer. Clin Cancer Res 17:3760–3770

    Article  PubMed  CAS  Google Scholar 

  16. Dodge-Kafka KL, Soughayer J, Pare GC et al (2005) The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways. Nature 437:574–578

    Article  PubMed  CAS  Google Scholar 

  17. Bradbury AW, Carter DC, Miller WR, Cho-Chung YS, Clair T (1994) Protein kinase A (PKA) regulatory subunit expression in colorectal cancer and related mucosa. Br J Cancer 69:738–742

    Article  PubMed  CAS  Google Scholar 

  18. Bold RJ, Alpard S, Ishizuka J, Townsend CM Jr, Thompson JC (1994) Growth-regulatory effect of gastrin on human colon cancer cell lines is determined by protein kinase a isoform content. Regul Pept 53:61–70

    Article  PubMed  CAS  Google Scholar 

  19. Nesterova MV, Johnson N, Cheadle C et al (2006) Autoantibody cancer biomarker: extracellular protein kinase A. Cancer Res 66:8971–8974

    Article  PubMed  CAS  Google Scholar 

  20. Hensley HH, Hannoun-Levi JM, Hachem P et al (2011) PKA knockdown enhances cell killing in response to radiation and androgen deprivation. Int J Cancer 128:962–973

    Article  PubMed  CAS  Google Scholar 

  21. Chen TC, Hinton DR, Zidovetzki R, Hofman FM (1998) Upregulation of the cAMP/PKA pathway inhibits proliferation, induces differentiation, and leads to apoptosis in malignant gliomas. Lab Invest 78:165–174

    PubMed  CAS  Google Scholar 

  22. Siddappa R, Mulder W, Steeghs I et al (2009) cAMP/PKA signaling inhibits osteogenic differentiation and bone formation in rodent models. Tissue Eng Part A 15:2135–2143

    Article  PubMed  CAS  Google Scholar 

  23. Loniewska B, Clark JS, Kaczmarczyk M et al (2012) Possible counter effect in newborns of 1936A>G (I646V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10. J Perinatol 32:230–234

    Article  PubMed  CAS  Google Scholar 

  24. Zukowski M, Bohatyrewicz R, Biernawska J et al (2009) Association of the A1936G (rs203462) of A-kinase anchoring protein 10 polymorphisms with QT interval prolongation during kidney transplantation. Transplant Proc 41:3036–3038

    Article  PubMed  CAS  Google Scholar 

  25. Kammerer S, Burns-Hamuro LL, Ma Y et al (2003) Amino acid variant in the kinase binding domain of dual-specific A kinase-anchoring protein 2: a disease susceptibility polymorphism. Proc Natl Acad Sci USA 100:4066–4071

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Professors Zhou and Sun for guiding this study, the members of Digestive Surgery Institution of West China Hospital for useful assistance and colleagues of the Department of Gastrointestinal Surgery for providing experimental specimens. This study was supported by the National Natural Science Founding of China (No. 30830100).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zongguang Zhou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, M., Zhang, D., Wang, R. et al. A-Kinase Anchoring Proteins 10 Expression in Relation to 2073A/G Polymorphism and Tumor Progression in Patients with Colorectal Cancer. Pathol. Oncol. Res. 19, 521–527 (2013). https://doi.org/10.1007/s12253-013-9612-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-013-9612-6

Keywords

Navigation