Molecular Backgrounds of ERAP1 Downregulation in Cervical Carcinoma
The antigen processing machinery (APM) plays an important role in immune recognition of virally infected and transformed cells. Defective expression of the APM component ERAP1 is associated with progression and poor clinical outcome in cervical carcinoma. However, the underlying mechanisms of ERAP1...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2015/367837 |
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| author | Akash M. Mehta Michelle Osse Sandra Kolkman-Uljee Gert Jan Fleuren Ekaterina S. Jordanova |
| author_facet | Akash M. Mehta Michelle Osse Sandra Kolkman-Uljee Gert Jan Fleuren Ekaterina S. Jordanova |
| author_sort | Akash M. Mehta |
| collection | DOAJ |
| description | The antigen processing machinery (APM) plays an important role in immune recognition of virally infected and transformed cells. Defective expression of the APM component ERAP1 is associated with progression and poor clinical outcome in cervical carcinoma. However, the underlying mechanisms of ERAP1 protein downregulation remain to be established. We investigated ERAP1 mRNA expression levels in 14 patients with established ERAP1 protein downregulation. To further examine the possible pretranscriptional mechanisms of ERAP1 downregulation, ERAP1 DNA mutation status was analyzed alongside existing data on various single nucleotide polymorphisms. Moreover, loss of heterozygosity at various loci in the ERAP1 gene was investigated. In cases with ERAP1 protein downregulation, ERAP1 mRNA quantities were found to be significantly lower than in a cohort with normal ERAP1 protein expression P=0.001. Loss of heterozygosity was demonstrated to occur in up to 50% of tumors with ERAP1 downregulation. Our data indicate that ERAP1 downregulation is associated with loss of heterozygosity. These data provide the first insight into in vivo mechanisms of ERAP1 downregulation in cervical carcinoma. |
| format | Article |
| id | doaj-art-522d966e65934cdcb25f45e73ec02394 |
| institution | OA Journals |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-522d966e65934cdcb25f45e73ec023942025-08-20T02:05:31ZengWileyAnalytical Cellular Pathology2210-71772210-71852015-01-01201510.1155/2015/367837367837Molecular Backgrounds of ERAP1 Downregulation in Cervical CarcinomaAkash M. Mehta0Michelle Osse1Sandra Kolkman-Uljee2Gert Jan Fleuren3Ekaterina S. Jordanova4Department of Pathology, Leiden University Medical Center, L1-Q, 2333 ZA Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, L1-Q, 2333 ZA Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, L1-Q, 2333 ZA Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, L1-Q, 2333 ZA Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, L1-Q, 2333 ZA Leiden, NetherlandsThe antigen processing machinery (APM) plays an important role in immune recognition of virally infected and transformed cells. Defective expression of the APM component ERAP1 is associated with progression and poor clinical outcome in cervical carcinoma. However, the underlying mechanisms of ERAP1 protein downregulation remain to be established. We investigated ERAP1 mRNA expression levels in 14 patients with established ERAP1 protein downregulation. To further examine the possible pretranscriptional mechanisms of ERAP1 downregulation, ERAP1 DNA mutation status was analyzed alongside existing data on various single nucleotide polymorphisms. Moreover, loss of heterozygosity at various loci in the ERAP1 gene was investigated. In cases with ERAP1 protein downregulation, ERAP1 mRNA quantities were found to be significantly lower than in a cohort with normal ERAP1 protein expression P=0.001. Loss of heterozygosity was demonstrated to occur in up to 50% of tumors with ERAP1 downregulation. Our data indicate that ERAP1 downregulation is associated with loss of heterozygosity. These data provide the first insight into in vivo mechanisms of ERAP1 downregulation in cervical carcinoma.http://dx.doi.org/10.1155/2015/367837 |
| spellingShingle | Akash M. Mehta Michelle Osse Sandra Kolkman-Uljee Gert Jan Fleuren Ekaterina S. Jordanova Molecular Backgrounds of ERAP1 Downregulation in Cervical Carcinoma Analytical Cellular Pathology |
| title | Molecular Backgrounds of ERAP1 Downregulation in Cervical Carcinoma |
| title_full | Molecular Backgrounds of ERAP1 Downregulation in Cervical Carcinoma |
| title_fullStr | Molecular Backgrounds of ERAP1 Downregulation in Cervical Carcinoma |
| title_full_unstemmed | Molecular Backgrounds of ERAP1 Downregulation in Cervical Carcinoma |
| title_short | Molecular Backgrounds of ERAP1 Downregulation in Cervical Carcinoma |
| title_sort | molecular backgrounds of erap1 downregulation in cervical carcinoma |
| url | http://dx.doi.org/10.1155/2015/367837 |
| work_keys_str_mv | AT akashmmehta molecularbackgroundsoferap1downregulationincervicalcarcinoma AT michelleosse molecularbackgroundsoferap1downregulationincervicalcarcinoma AT sandrakolkmanuljee molecularbackgroundsoferap1downregulationincervicalcarcinoma AT gertjanfleuren molecularbackgroundsoferap1downregulationincervicalcarcinoma AT ekaterinasjordanova molecularbackgroundsoferap1downregulationincervicalcarcinoma |