title: 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.
authors.affiliation: Institute of Pathology, University Hospital Erlangen, Krankenhausstr. 8-10, 91054 Erlangen, Germany. christine.stoehr@ukerlangen.de
authors.forename: Christine G
authors.initials: CG
authors.lastname: Stoehr
authors.forename: Maike
authors.initials: M
authors.lastname: Buettner-Herold
authors.forename: Esther
authors.initials: E
authors.lastname: Kamphausen
authors.forename: Simone
authors.initials: S
authors.lastname: Bertz
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
mesh_terms: D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007668:Kidney / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D015778:Minor Histocompatibility Antigens; D019139:Tumor Escape
chemical_list: D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D007371:Interferon-gamma; D000626:Aminopeptidases; C464841:ERAP1 protein, human; C503944:ERAP2 protein, human
keywords: ERAP; HLA class I; Renal cell carcinoma; immune escape