Resistance to Platinum-Containing Chemotherapy in Testicular Germ Cell Tumors Is Associated with Downregulation of the Protein Kinase SRPK1
Male germ cell tumors (GCTs) are extremely sensitive to platinum-containing chemotherapy, with only 10% of patients showing therapy resistance. However, the biological basis of the high curability of disseminated GCTs by chemotherapy is still unknown. Recently, we demonstrated that the mammalian ser...
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| Format: | Article |
| Language: | English |
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Elsevier
2004-07-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558604800770 |
| _version_ | 1818516428107546624 |
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| author | Paul W. Schenk Hans Stoop Carsten Bokemeyer Frank Mayer Gerrit Stoter J. Wolter Oosterhuis Erik Wiemer Leendert H.J. Looijenga Kees Nooter |
| author_facet | Paul W. Schenk Hans Stoop Carsten Bokemeyer Frank Mayer Gerrit Stoter J. Wolter Oosterhuis Erik Wiemer Leendert H.J. Looijenga Kees Nooter |
| author_sort | Paul W. Schenk |
| collection | DOAJ |
| description | Male germ cell tumors (GCTs) are extremely sensitive to platinum-containing chemotherapy, with only 10% of patients showing therapy resistance. However, the biological basis of the high curability of disseminated GCTs by chemotherapy is still unknown. Recently, we demonstrated that the mammalian serine/arginine rich protein-specific kinase 1 (SRPK1) is a cisplatinsensitive gene, inactivation of which leads to cisplatin resistance. Because, in mammalians, the expression of SRPK1 is preferentially high in testicular tissues, cisplatin responsiveness of male GCTs might be associated with SRPKi levels. In the present study, we monitored SRPK1 protein expression in a unique series of nonseminomatous GCTs by immunohistochemistry. Randomly selected GCTs (n = 70) and tumors from patients responding to standard chemotherapy (n = 20) generally showed strong SRPKi staining. In contrast, expression in refractory GCTs (n = 20) as well as in GCTs from poor-prognosis patients responding to high-dose chemotherapy only (n = 11) was significantly lower (two-sided Wilcoxon rank sum test: P < .001). In conclusion, our data suggest that SRPK1 expression might be an important prognostic indicator for the chemoresponsiveness of nonseminomatous GCTs. |
| first_indexed | 2024-12-11T00:41:59Z |
| format | Article |
| id | doaj.art-72cf020a20f24710ad08aec719857499 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-11T00:41:59Z |
| publishDate | 2004-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-72cf020a20f24710ad08aec7198574992022-12-22T01:26:53ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022004-07-016429730110.1593/neo.03406Resistance to Platinum-Containing Chemotherapy in Testicular Germ Cell Tumors Is Associated with Downregulation of the Protein Kinase SRPK1Paul W. Schenk0Hans Stoop1Carsten Bokemeyer2Frank Mayer3Gerrit Stoter4J. Wolter Oosterhuis5Erik Wiemer6Leendert H.J. Looijenga7Kees Nooter8Departments of Medical Oncology, Erasmus-MC, Rotterdam, The NetherlandsDepartments of Pathology/Laboratory for Experimental Patho-Oncology, Erasmus-MC, Rotterdam, The NetherlandsDepartment of Oncology, Hematology, and Rheumatology, University of Tuebingen Medical Center, Tuebingen, GermanyDepartment of Oncology, Hematology, and Rheumatology, University of Tuebingen Medical Center, Tuebingen, GermanyDepartments of Medical Oncology, Erasmus-MC, Rotterdam, The NetherlandsDepartments of Pathology/Laboratory for Experimental Patho-Oncology, Erasmus-MC, Rotterdam, The NetherlandsDepartments of Medical Oncology, Erasmus-MC, Rotterdam, The NetherlandsDepartments of Pathology/Laboratory for Experimental Patho-Oncology, Erasmus-MC, Rotterdam, The NetherlandsDepartments of Medical Oncology, Erasmus-MC, Rotterdam, The NetherlandsMale germ cell tumors (GCTs) are extremely sensitive to platinum-containing chemotherapy, with only 10% of patients showing therapy resistance. However, the biological basis of the high curability of disseminated GCTs by chemotherapy is still unknown. Recently, we demonstrated that the mammalian serine/arginine rich protein-specific kinase 1 (SRPK1) is a cisplatinsensitive gene, inactivation of which leads to cisplatin resistance. Because, in mammalians, the expression of SRPK1 is preferentially high in testicular tissues, cisplatin responsiveness of male GCTs might be associated with SRPKi levels. In the present study, we monitored SRPK1 protein expression in a unique series of nonseminomatous GCTs by immunohistochemistry. Randomly selected GCTs (n = 70) and tumors from patients responding to standard chemotherapy (n = 20) generally showed strong SRPKi staining. In contrast, expression in refractory GCTs (n = 20) as well as in GCTs from poor-prognosis patients responding to high-dose chemotherapy only (n = 11) was significantly lower (two-sided Wilcoxon rank sum test: P < .001). In conclusion, our data suggest that SRPK1 expression might be an important prognostic indicator for the chemoresponsiveness of nonseminomatous GCTs.http://www.sciencedirect.com/science/article/pii/S1476558604800770Chemotherapy resistancegerm cell tumorschemotherapy sensitivityprotein kinase SRPK1immunohistochemistry |
| spellingShingle | Paul W. Schenk Hans Stoop Carsten Bokemeyer Frank Mayer Gerrit Stoter J. Wolter Oosterhuis Erik Wiemer Leendert H.J. Looijenga Kees Nooter Resistance to Platinum-Containing Chemotherapy in Testicular Germ Cell Tumors Is Associated with Downregulation of the Protein Kinase SRPK1 Neoplasia: An International Journal for Oncology Research Chemotherapy resistance germ cell tumors chemotherapy sensitivity protein kinase SRPK1 immunohistochemistry |
| title | Resistance to Platinum-Containing Chemotherapy in Testicular Germ Cell Tumors Is Associated with Downregulation of the Protein Kinase SRPK1 |
| title_full | Resistance to Platinum-Containing Chemotherapy in Testicular Germ Cell Tumors Is Associated with Downregulation of the Protein Kinase SRPK1 |
| title_fullStr | Resistance to Platinum-Containing Chemotherapy in Testicular Germ Cell Tumors Is Associated with Downregulation of the Protein Kinase SRPK1 |
| title_full_unstemmed | Resistance to Platinum-Containing Chemotherapy in Testicular Germ Cell Tumors Is Associated with Downregulation of the Protein Kinase SRPK1 |
| title_short | Resistance to Platinum-Containing Chemotherapy in Testicular Germ Cell Tumors Is Associated with Downregulation of the Protein Kinase SRPK1 |
| title_sort | resistance to platinum containing chemotherapy in testicular germ cell tumors is associated with downregulation of the protein kinase srpk1 |
| topic | Chemotherapy resistance germ cell tumors chemotherapy sensitivity protein kinase SRPK1 immunohistochemistry |
| url | http://www.sciencedirect.com/science/article/pii/S1476558604800770 |
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