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Engrailed-2 is down-regulated but also ectopically expressed in clear cell renal cell carcinoma

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Abstract

Engrailed-2 (EN2), a member of the homeobox family of genes, encodes a homeodomain-containing transcription factor that is thought to be a potential oncogene in a number of cancers. Because the role of EN2 in clear cell renal cell carcinoma (CCRCC) has not been determined, we investigated its expression in CCRCC tissues and cell lines. Using immunohistochemical (IHC) staining, we found that EN2 protein was expressed in normal renal cells and tubules, but was frequently down-regulated in tissues from patients with CCRCC and in CCRCC cell lines. In addition, we found that EN2, which functions in the nucleus, was completely localized to the cytoplasm of CCRCC cells as detected by IHC and immunofluorescence staining. Furthermore, expression of EN2 protein was negatively correlated with increasing histological grade of CCRCC tumors (P = 0.003). The exact role of EN2 expression in renal carcinoma carcinogenesis requires further investigation.

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Abbreviations

CCRCC:

Clear cell renal cell carcinoma

EN2:

Engrailed 2

RT-qPCR:

Real-time quantitative polymerase chain reaction

IHC:

Immunohistochemistry

References

  1. Ljungberg B, Campbell SC, Cho HY, Jacqmin D, Lee JE, Weikert S, Kiemeney LA (2011) The epidemiology of renal cell carcinoma. Eur Urol 60:615–621

    Article  PubMed  Google Scholar 

  2. Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C (2008) Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev 34:193–205

    Article  PubMed  Google Scholar 

  3. Rini BI, Campbell SC, Escudier B (2009) Renal cell carcinoma. Lancet 373:1119–1132

    Article  CAS  PubMed  Google Scholar 

  4. McDermott DF, Rini BI (2007) Immunotherapy for metastatic renal cell carcinoma. BJU Int 99:1282–1288

    Article  CAS  PubMed  Google Scholar 

  5. Escudier B, Szczylik C, Porta C, Gore M (2012) Treatment selection in metastatic renal cell carcinoma: expert consensus. Nat Rev Clin Oncol 9:327–337

    Article  CAS  PubMed  Google Scholar 

  6. Martin NL, Saba-El-Leil MK, Sadekova S, Meloche S, Sauvageau G (2005) EN2 is a candidate oncogene in human breast cancer. Oncogene 24:6890–6901

    Article  CAS  PubMed  Google Scholar 

  7. Morgan R, Boxall A, Bhatt A, Bailey M, Hindley R, Langley S, Whitaker HC, Neal DE, Ismail M, Whitaker H, Annels N, Michael A, Pandha H (2011) Engrailed-2(EN2): a highly specific urinary biomarker for the early diagnosis of prostate cancer. Clin Cancer Res 17:1090–1098

    Article  CAS  PubMed  Google Scholar 

  8. Cui Y, Wu J, Zong M, Song G, Jia Q, Jiang J, Han J (2009) Proteomic profiling in pancreatic cancer with and without lymph node metastasis. Int J Cancer 124:1614–1621

    Article  CAS  PubMed  Google Scholar 

  9. Joliot A, Maizel A, Rosenberg D, Trembleau A, Dupas S, Volovitch M, Prochiantz A (1998) Identification of a signal sequence necessary for the unconventional secretion of engrailed homeoprotein. Curr Biol 8:856–863

    Article  CAS  PubMed  Google Scholar 

  10. Maize A, Tassetto M, Filho O, Cochet C, Prochiantz A, Joliot A (2002) Engrailed homeoprotein secretion is a regulated process. Development 129:3545–3553

    Google Scholar 

  11. Garcia-Bellido A, Santamaria P (1972) Developmental analysis of the wing disc in the mutant engrailed of drosophila melanogaster. Genetics 72:87–104

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Bose SK, Bullard RS, Donald CD (2008) Oncogenic role of engrailed-2 (En-2) in prostate cancer cell growth and survival. Transl Oncogenomics 3:37–43

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Pandha H, Sorensen KD, Orntoft TF, Langley S, Hoyer S, Borre M, Morgan R (2012) Urinary engrailed-2 (EN2) levels predict tumour volume in men undergoing radical prostatectomy for prostate cancer. BJU int 110:E287–E292

    Article  CAS  PubMed  Google Scholar 

  14. Morgan R (2006) Engrailed: complexity and economy of a multi-functional transcription factor. FEBS Lett 580:2531–2533

    Article  CAS  PubMed  Google Scholar 

  15. Polakis P (2000) Wnt signaling and cancer. Gene Dev 14:1837–1851

    CAS  PubMed  Google Scholar 

  16. Hart M, Concordet JP, Lassot I, Albert I, Santos RD, Durand H, Perret C, Rubinfeld B, Margottin F, Benarous R, Polakis P (1999) The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Curr Biol 9:207–210

    Article  CAS  PubMed  Google Scholar 

  17. Yamamoto H, Kishida S, Kishida M, Ikeda S, Takada S, Kikuchi A (1999) Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3β regulates its stability. J Biol Chem 274:10681–10684

    Article  CAS  PubMed  Google Scholar 

  18. Katoh M (2007) WNT signaling pathway and stem cell signaling network[J]. Clin Cancer Res 13:4042–4045

    Article  CAS  PubMed  Google Scholar 

  19. Sabrina FK, Susanne B, Kamar H, Fichtner D, Wedlich D, Gradl D (2010) En2, Pax2/5 and Tcf-4 transcription factors cooperate in patterning the Xenopus brain. Dev Biol 340:318–328

    Article  Google Scholar 

  20. Shah N, Sukumar S (2010) The Hox genes and their roles in oncogenesis. Nat Rev Cancer 10:361–371

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Hong Li for help in sample collection as well as Professor Guang-yu Jiang, Dr Bin Du, and Prof Huan Zhang for technical assistance. We thank our patients for their support and cooperation for this study. This study was supported by the Key specialist of Guangdong Provincial 12th Five-Year Plan (No. 201220) and Guangzhou Municipal Health Bureau Grant (N0. 20121A011159).

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Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Jinan University, No. 613 Huang Pu Rd, Guangzhou, 510630, China

    Cai-yong Lai, Bin Pan, Wei-bo Liang, Jie Chen, Dong-ming Ye, Ji-Nan Guo, Li Li & Ze-xuan Su

  2. Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China

    Yun Luo

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  1. Cai-yong Lai
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  2. Bin Pan
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Correspondence to Ze-xuan Su.

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Lai, Cy., Pan, B., Luo, Y. et al. Engrailed-2 is down-regulated but also ectopically expressed in clear cell renal cell carcinoma. Mol Biol Rep 41, 3651–3657 (2014). https://doi.org/10.1007/s11033-014-3229-z

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  • DOI: https://doi.org/10.1007/s11033-014-3229-z

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