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Comparative expression profiling for human endoplasmic reticulum-resident aminopeptidases 1 and 2 in normal kidney versus distinct renal cell carcinoma subtypes.

Abstract
Altered expression of the ER-resident aminopeptidases ERAP1 and ERAP2 might play an important role in shaping the MHC class I-presented peptide repertoire, but their function in tumors has not been determined in detail. Thus, the expression of ERAP1, ERAP2 and HLA class I heavy chain (HC) was analysed in various renal tumor types and corresponding kidney parenchyma by immunohistochemistry. Additionally, comparative expression profilings of untreated versus interferon (IFN)-γ-treated RCC cell lines were performed applying qRT-PCR, Western blot and/or flow cytometry. Normal kidney tissues showed strong ERAP1 staining in the proximal tubules of 57.4 % of cases, in the distal tubules of 94.3 % of cases and in the medulla of 88.6 % of cases, whereas high ERAP2 levels were observed in the medulla of 77.1 % of cases and in both, proximal and distal tubules of about 88 % of cases. Imbalanced, downregulated and RCC subtype-specific ERAP1 or ERAP2 expression was detected in 12.7 % or 43.8 % of samples analyzed, respectively. A coordinated downregulation of ERAPs was found in 4.8 %, an upregulation of ERAP1 or ERAP2 in 22.8 % or 2.0 % of RCC lesions. No association exists between ERAP and HLA class I HC expression for any tissue type. A heterogeneous constitutive ERAP expression pattern was also detected in RCC cell lines with lower ERAP2 than ERAP1 expression levels, which was in 11/17 RCC cell lines inducible by IFN-γ. Conclusively, ERAP1 and ERAP2 might be involved in the development of immune escape mechanisms of RCC.
AuthorsChristine G Stoehr, Maike Buettner-Herold, Esther Kamphausen, Simone Bertz, Arndt Hartmann, Barbara Seliger
JournalInternational journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 6 Issue 6 Pg. 998-1008 ( 2013) ISSN: 1936-2625 [Electronic] United States
PMID23696916 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • Histocompatibility Antigens Class I
  • Minor Histocompatibility Antigens
  • Interferon-gamma
  • Aminopeptidases
  • ERAP1 protein, human
  • ERAP2 protein, human
Topics
  • Aminopeptidases (genetics, metabolism)
  • Biomarkers, Tumor (genetics, metabolism)
  • Carcinoma, Renal Cell (enzymology, genetics, immunology, pathology)
  • Case-Control Studies
  • Cell Line, Tumor
  • Endoplasmic Reticulum (enzymology, pathology)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histocompatibility Antigens Class I (metabolism)
  • Humans
  • Interferon-gamma (metabolism)
  • Kidney (enzymology, immunology, pathology)
  • Kidney Neoplasms (enzymology, genetics, immunology, pathology)
  • Male
  • Minor Histocompatibility Antigens
  • Tumor Escape

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