Skip to main content

Advertisement

SpringerLink
Log in

Aberrant SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas

  • Research Article
  • Published:
Tumor Biology

Summary

Sarco (endo)plasmic reticulum Ca2+-ATPase (SERCAs) 3 is involved in calcium mobilization from endoplasmic reticulum into cytosol and closely links to metabolism, neuronal plasticity, gene transcription, cell growth, differentiation, apoptosis, protein folding, and carcinogenesis. To clarify the role of SERCA3 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa (NNM), and metastatic lymph node. SERCA3 expression was studied in gastric carcinoma tissue and cell lines by Western blot, reverse transcriptase-polymerase chain reaction, or immunofluorescence. The results demonstrated that SERCA3 was distinctively expressed in GES-1, AGS, BGC-823, GT-3TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, and STKM-2 at both mRNA and protein levels. The carcinomas showed higher SERCA3 mRNA expression than the matched NNM by real-time PCR and ISH (P < 0.05). Immunohistochemically, SERCA3 expression was decreased from gastric NNM, primary to metastatic carcinoma (P < 0.05). SERCA3 expression was negatively related to depth of invasion, distant metastasis, and tumor node metastasis (TNM) staging (P < 0.05), but not to age, sex, lymphatic or venous invasion, or lymph node metastasis (P > 0.05). Kaplan–Meier analysis indicated that SERCA3 expression was positively associated with favorable prognosis of the patients with gastric carcinoma (P < 0.05). Cox’s proportional hazard model indicated that venous invasion, distant metastasis and TNM staging (P < 0.05) were independent prognostic factors for gastric carcinomas. It was suggested that downregulated SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas. It might be employed to indicate the pathobiological behaviors and prognosis of gastric carcinomas.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Arbabian A, Brouland JP, Gélébart P, Kovàcs T, Bobe R, Enouf J, et al. Endoplasmic reticulum calcium pumps and cancer. Biofactors. 2011;37:139–49.

    Article  PubMed  CAS  Google Scholar 

  2. Arredouani A, Guiot Y, Jonas JC, Liu LH, Nenquin M, Pertusa JA, et al. SERCA3 ablation does not impair insulin secretion but suggests distinct roles of different sarcoendoplasmic reticulum Ca(2+) pumps for Ca(2+) homeostasis in pancreatic beta-cells. Diabetes. 2002;51:3245–53.

    Article  PubMed  CAS  Google Scholar 

  3. Baba-Aïssa F, Raeymaekers L, Wuytack F, Callewaert G, Dode L, Missiaen L, et al. Purkinje neurons express the SERCA3 isoform of the organellar type Ca(2+)-transport ATPase. Brain Res Mol Brain Res. 1996;41:169–74.

    Article  PubMed  Google Scholar 

  4. Brouland JP, Gélébart P, Kovàcs T, Enouf J, Grossmann J, Papp B. The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is an early event during the multistep process of colon carcinogenesis. Am J Pathol. 2005;167:233–42.

    Article  PubMed  CAS  Google Scholar 

  5. Brouland JP, Valleur P, Papp B. Expression of SERCA pumps during cell differentiation and tumorigenesis: application to colonic carcinogenesis. Ann Pathol. 2006;26:159–72.

    Article  PubMed  Google Scholar 

  6. Chandrasekera PC, Kargacin ME, Deans JP, Lytton J. Determination of apparent calcium affinity for endogenously expressed human sarco(endo)plasmic reticulum calcium-ATPase isoform SERCA3. Am J Physiol Cell Physiol. 2009;296:C1105–14.

    Article  PubMed  CAS  Google Scholar 

  7. Gélébart P, Kovács T, Brouland JP, van Gorp R, Grossmann J, Rivard N, et al. Expression of endomembrane calcium pumps in colon and gastric cancer cells. Induction of SERCA3 expression during differentiation. J Biol Chem. 2002;277:26310–20.

    Article  PubMed  Google Scholar 

  8. Hovnanian A. SERCA pumps and human diseases. Subcell Biochem. 2007;45:337–63.

    Article  PubMed  CAS  Google Scholar 

  9. Kao J, Fortner CN, Liu LH, Shull GE, Paul RJ. Ablation of the SERCA3 gene alters epithelium-dependent relaxation in mouse tracheal smooth muscle. Am J Physiol Lung Cell Mol Physiol. 1999;277:L264–70.

    CAS  Google Scholar 

  10. Kelley JR, Duggan JM. Gastric cancer epidemiology and risk factors. J Clin Epidemiol. 2003;56:1–9.

    Article  PubMed  Google Scholar 

  11. Kumada T, Tsuneyama K, Hatta H, Ishizawa S, Takano Y. Improved 1-h rapid immunostaining method using intermittent microwave irradiation: practicability based on 5 years application in Toyama Medical and Pharmaceutical University Hospital. Mod Pathol. 2004;17:1141–9.

    Article  PubMed  Google Scholar 

  12. Li W, Murai Y, Okada E, Matsui K, Hayashi S, Horie M, et al. Modified and simplified western blotting protocol: use of intermittent microwave irradiation (IMWI) and 5 % skim milk to improve binding specificity. Pathol Int. 2002;52:234–8.

    Article  PubMed  Google Scholar 

  13. Liu LH, Paul RJ, Sutliff RL, Miller ML, Lorenz JN, Pun RY, et al. Defective endothelium- dependent relaxation of vascular smooth muscle and endothelial cell Ca2+ signalling in mice lacking sarco(endo)plasmic reticulum Ca2+-ATPase isoform 3. J Biol Chem. 1997;272:30538–45.

    Article  PubMed  CAS  Google Scholar 

  14. Roe MW, Philipson LH, Frangakis CJ, Kuznetsov A, Mertz RJ, Lancaster ME, et al. Defective glucose-dependent endoplasmic reticulum Ca2+ sequestration in diabetic mouse islets of Langerhans. J Biol Chem. 1994;269:18279–82.

    PubMed  CAS  Google Scholar 

  15. Sobin LH, Wittekind CH. TNM classification of malignant tumours. 6th ed. Hoboken: Wiley; 2002.

    Google Scholar 

  16. Varadi A, Lebel L, Hashim Y, Mehta Z, Ashcroft SJH, Turner R. Sequence variants of the sarco(endo)plasmic reticulum Ca2+-transport ATPase 3 gene (SERCA3) in Caucasian type II diabetic patients (UK Prospective Diabetes Study 48). Diabetologia. 1999;42:1240–3.

    Article  PubMed  CAS  Google Scholar 

  17. Wuytack F, Dode L, Baba-Aissa F, Raeymaekers L. The SERCA3-type of organellar Ca2+ pumps. Biosci Rep. 1995;15:299–306.

    Article  PubMed  CAS  Google Scholar 

  18. Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Miwa S, et al. Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas. Virchows Arch. 2008;452:525–34.

    Article  PubMed  CAS  Google Scholar 

  19. Zheng HC, Takahashi H, Li XH, Hara T, Masuda S, Guan YF, et al. Downregulated parafibromin expression is a promising marker for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas. Virchows Arch. 2008;452:147–55.

    Article  PubMed  CAS  Google Scholar 

  20. Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Miwa S, et al. Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan: an immunostaining study on the tissue microarray. J Clin Pathol. 2007;60:273–7.

    Article  PubMed  CAS  Google Scholar 

  21. Zheng HC, Zheng YS, Li XH, Takahashi H, Hara T, Masuda S, et al. Arp2/3 overexpression contributed to pathogenesis, growth and invasion of gastric carcinoma. Anticancer Res. 2008;28:2225–32.

    PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Shenyang Outstanding Talent Foundation of China; Shenyang Science and Technology grant (F11-264-1-10); Natural Scientific Foundation of China (no. 81001093, no. 81101886, no. 81172371); a Project Supported by Scientific Research Fund of Liaoning Provincial Education Department (L2010649); Specialized Research Fund for the Doctoral Program of Higher Education (no. 20102104120026) and Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports and Technology of Japan (23659958).

Author information

Authors and Affiliations

  1. Department of Pathophysiology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China

    Xiao-yan Xu

  2. Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China

    Wen-feng Gou, Xue Yang, Guo-li Wang & Hua-chuan Zheng

  3. Clinical Research Institute, Kanagawa Cancer Center, Yokohama, 241-0815, Japan

    Hiroyuki Takahashi & Yasuo Takano

  4. Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China

    Miao Yu & Xiao-yun Mao

Authors
  1. Xiao-yan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wen-feng Gou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xue Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guo-li Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroyuki Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Miao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiao-yun Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yasuo Takano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hua-chuan Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hua-chuan Zheng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xu, Xy., Gou, Wf., Yang, X. et al. Aberrant SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas. Tumor Biol. 33, 1845–1854 (2012). https://doi.org/10.1007/s13277-012-0444-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0444-x

Keywords

Search

Navigation