Skip to main content
SpringerLink
Log in

SOCS5 and SOCS6 have similar expression patterns in normal and cancer tissues

  • Research Article
  • Published:
Tumor Biology

Abstract

In the present study, we investigated mRNA expression patterns of both SOCS5 and SOCS6 in various normal and cancer tissues using a commercially available Cancer Profiling Array. We found that SOCS5 and SOCS6 had similar expression patterns in most cancer and healthy individuals, suggesting that these two genes are transcriptionally co-regulated. Tissue-specific up- or down-regulation of SOCS5 and SOCS6 was observed in several cancer tissues. Most importantly, thyroid gland cancer tissues exhibited large reductions of both SOCS5 and SOCS6 expressions. In addition, mRNA and protein levels of SOCS6 were down-regulated in liver cancer tissues. The results from our study may contribute to understanding SOCS5 and SOCS6 expression regulation in various cancer tissues, and show that these two factors may be used for diagnosing cancer.

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

Similar content being viewed by others

Abbreviations

PSL:

Photostimulated luminescence

SOCS:

Suppressors of cytokine signaling

CIS:

Cytokine-inducible SH2-containing protein

ORF:

Open reading frame

Stat:

Signal transducer and activator of transcription

Jak:

Janus kinase

References

  1. Kamizono S, Hanada T, Yasukawa H, Minoguchi S, Kato R, Minoguchi M, Hattori K, Hatakeyama S, Yada M, Morita S, Kitamura T, Kato H, Nakayama K, Yoshimura A. The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2. J Biol Chem. 2001;276:12530–8.

    Article  PubMed  CAS  Google Scholar 

  2. Zhang JG, Metcalf D, Rakar S, Asimakis M, Greenhalgh CJ, Willson TA, Starr R, Nicholson SE, Carter W, Alexander WS, Hilton DJ, Nicola NA. The SOCS box of suppressor of cytokine signaling-1 is important for inhibition of cytokine action in vivo. Proc Natl Acad Sci U S A. 2001;98:13261–5.

    Article  PubMed  CAS  Google Scholar 

  3. Hilton DJ, Richardson RT, Alexander WS, Viney EM, Willson TA, Sprigg NS, Starr R, Nicholson SE, Metcalf D, Nicola NA. Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc Natl Acad Sci U S A. 1998;95:114–9.

    Article  PubMed  CAS  Google Scholar 

  4. Wormald S, Hilton DJ. Inhibitors of cytokine signal transduction. J Biol Chem. 2004;279:821–4.

    Article  PubMed  CAS  Google Scholar 

  5. Krebs DL, Hilton DJ. Socs: physiological suppressors of cytokine signaling. J Cell Sci. 2000;113(Pt 16):2813–9.

    PubMed  CAS  Google Scholar 

  6. Kubo M, Hanada T, Yoshimura A. Suppressors of cytokine signaling and immunity. Nat Immunol. 2003;4:1169–76.

    Article  PubMed  CAS  Google Scholar 

  7. Greenhalgh CJ, Miller ME, Hilton DJ, Lund PK. Suppressors of cytokine signaling: relevance to gastrointestinal function and disease. Gastroenterology. 2002;123:2064–81.

    Article  PubMed  CAS  Google Scholar 

  8. O'Sullivan LA, Liongue C, Lewis RS, Stephenson SE, Ward AC. Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol Immunol. 2007;44:2497–506.

    Article  PubMed  Google Scholar 

  9. Flores-Morales A, Greenhalgh CJ, Norstedt G, Rico-Bautista E. Negative regulation of growth hormone receptor signaling. Mol Endocrinol. 2006;20:241–3.

    Article  PubMed  CAS  Google Scholar 

  10. Dimitriou ID, Clemenza L, Scotter AJ, Chen G, Guerra FM, Rottapel R. Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins. Immunol Rev. 2008;224:265–83.

    Article  PubMed  CAS  Google Scholar 

  11. Sutherland KD, Lindeman GJ, Visvader JE. Knocking off SOCS genes in the mammary gland. Cell Cycle. 2007;6:799–803.

    Article  PubMed  CAS  Google Scholar 

  12. Lee KH, Moon KJ, Kim HS, Yoo BC, Park S, Lee H, Kwon S, Lee ES, Yoon S. Increased cytoplasmic levels of CIS, SOCS1, SOCS2, or SOCS3 are required for nuclear translocation. FEBS Lett. 2008;582:2319–24.

    Article  PubMed  CAS  Google Scholar 

  13. Evans MK, Yu CR, Lohani A, Mahdi RM, Liu X, Trzeciak AR, Egwuagu CE. Expression of SOCS1 and SOCS3 genes is differentially regulated in breast cancer cells in response to proinflammatory cytokine and growth factor signals. Oncogene. 2007;26:1941–8.

    Article  PubMed  CAS  Google Scholar 

  14. Liu XH, Xu SB, Yuan J, Li BH, Zhang Y, Yuan Q, Li PD, Li F, Zhang WJ. Defective interleukin-4/Stat6 activity correlates with increased constitutive expression of negative regulators SOCS-3, SOCS-7, and CISH in colon cancer cells. J Interferon Cytokine Res. 2009;29:809–16.

    Article  PubMed  CAS  Google Scholar 

  15. Sasi W, Jiang WG, Sharma A, Mokbel K. Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer. BMC Cancer. 2010;10:178.

    Article  PubMed  Google Scholar 

  16. Hwang MN, Min CH, Kim HS, Lee H, Yoon KA, Park SY, Lee ES, Yoon S. The nuclear localization of SOCS6 requires the n-terminal region and negatively regulates Stat3 protein levels. Biochem Biophys Res Commun. 2007;360:333–8.

    Article  PubMed  CAS  Google Scholar 

  17. Storojeva I, Boulay JL, Ballabeni P, Buess M, Terracciano L, Laffer U, Mild G, Herrmann R, Rochlitz C. Prognostic and predictive relevance of DNAM-1, SOCS6 and CADH-7 genes on chromosome 18q in colorectal cancer. Oncology. 2005;68:246–55.

    Article  PubMed  CAS  Google Scholar 

  18. Lai RH, Hsiao YW, Wang MJ, Lin HY, Wu CW, Chi CW, Li AF, Jou YS, Chen JY. SOCS6, down-regulated in gastric cancer, inhibits cell proliferation and colony formation. Cancer Lett. 2010;288:75–85.

    Article  PubMed  CAS  Google Scholar 

  19. Kremer BE, Adang LA, Macara IG. Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of nck mediated by SOCS7. Cell. 2007;130:837–50.

    Article  PubMed  CAS  Google Scholar 

  20. Calvisi DF, Ladu S, Gorden A, Farina M, Lee JS, Conner EA, Schroeder I, Factor VM, Thorgeirsson SS. Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma. J Clin Invest. 2007;117:2713–22.

    Article  PubMed  CAS  Google Scholar 

  21. Zhumabayeva B, Diatchenko L, Chenchik A, Siebert PD. Use of smart-generated cdna for gene expression studies in multiple human tumors. Biotechniques. 2001;30:158–63.

    PubMed  CAS  Google Scholar 

  22. Yoon S, Govind CK, Qiu H, Kim SJ, Dong J, Hinnebusch AG. Recruitment of the ArgR/Mcm1p repressor is stimulated by the activator Gcn4p: a self-checking activation mechanism. Proc Natl Acad Sci U S A. 2004;101:11713–8.

    Article  PubMed  CAS  Google Scholar 

  23. Kim SS, Cao L, Lim SC, Li C, Wang RH, Xu X, Bachelier R, Deng CX. Hyperplasia and spontaneous tumor development in the gynecologic system in mice lacking the BRCA1-DELTA11 isoform. Mol Cell Biol. 2006;26:6983–92.

    Article  PubMed  CAS  Google Scholar 

  24. Hong S, Yoon S. Mcm1p binding sites in the ARG1 promoter positively regulate ARG1 transcription and S. cerevisiae growth in the absence of arginine and Gcn4p. Amino Acids. 2011;40:623–31.

    Article  PubMed  CAS  Google Scholar 

  25. Yang KJ, Shin S, Piao L, Shin E, Li Y, Park KA, Byun HS, Won M, Hong J, Kweon GR, Hur GM, Seok JH, Chun T, Brazil DP, Hemmings BA, Park J. Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src involves tyrosine phosphorylation of pdk1 and Src homology 2 domain binding. J Biol Chem. 2008;283:1480–91.

    Article  PubMed  CAS  Google Scholar 

  26. Puxeddu E, Knauf JA, Sartor MA, Mitsutake N, Smith EP, Medvedovic M, Tomlinson CR, Moretti S, Fagin JA. RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation of genes involved in regulation of the immune response. Endocr Relat Cancer. 2005;12:319–34.

    Article  PubMed  CAS  Google Scholar 

  27. Park ES, Kim H, Suh JM, Park SJ, You SH, Chung HK, Lee KW, Kwon OY, Cho BY, Kim YK, Ro HK, Chung J, Shong M. Involvement of JAK/STAT (janus kinase/signal transducer and activator of transcription) in the thyrotropin signaling pathway. Mol Endocrinol. 2000;14:662–70.

    Article  PubMed  CAS  Google Scholar 

  28. Park ES, Kim H, Suh JM, Park SJ, Kwon OY, Kim YK, Ro HK, Cho BY, Chung J, Shong M. Thyrotropin induces SOCS-1 (suppressor of cytokine signaling-1) and SOCS-3 in FRTL-5 thyroid cells. Mol Endocrinol. 2000;14:440–8.

    Article  PubMed  CAS  Google Scholar 

  29. Francipane MG, Eterno V, Spina V, Bini M, Scerrino G, Buscemi G, Gulotta G, Todaro M, Dieli F, De Maria R, Stassi G. Suppressor of cytokine signaling 3 sensitizes anaplastic thyroid cancer to standard chemotherapy. Cancer Res. 2009;69:6141–8.

    Article  PubMed  CAS  Google Scholar 

  30. Zaitseva II, Hultcrantz M, Sharoyko V, Flodstrom-Tullberg M, Zaitsev SV, Berggren PO. Suppressor of cytokine signaling-1 inhibits caspase activation and protects from cytokine-induced beta cell death. Cell Mol Life Sci. 2009;66:3787–95.

    Article  PubMed  CAS  Google Scholar 

  31. Horndasch M, Culig Z. SOCS-3 antagonizes pro-apoptotic effects of TRAIL and resveratrol in prostate cancer cells. Prostate. 2011;71:1357–66.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the Basic Science Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2009-0070791).

Author information

Authors and Affiliations

  1. Research Institute, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do, 411-764, South Korea

    Sungpil Yoon, Sang Soo Kim & Ju-Hwa Kim

  2. Bio Research Laboratory 1, Life Science Research Institute, Daewoong Pharmaceutical Co., Yongin, Gyeonggi-do, South Korea

    Young-Su Yi

  3. Department of Pathology, Collage of Medicine, The Catholic University of Korea, Seoul, South Korea

    Won Sang Park & Suk Woo Nam

Authors
  1. Sungpil Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Young-Su Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sang Soo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ju-Hwa Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Won Sang Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Suk Woo Nam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sungpil Yoon.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 50 kb)

ESM 2

(JPEG 21 kb)

High resolution image (TIFF 2221 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoon, S., Yi, YS., Kim, S.S. et al. SOCS5 and SOCS6 have similar expression patterns in normal and cancer tissues. Tumor Biol. 33, 215–221 (2012). https://doi.org/10.1007/s13277-011-0264-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-011-0264-4

Keywords

Search

Navigation