title: The kinase RSK2 modulates the sensitivity of ovarian cancer cells to cisplatin.
abstract: Platinum-based chemotherapy (e.g. cisplatin, carboplatin) is standard of care for many types of cancer including ovarian cancer, however, the efficacy of treatment is hampered by the development of therapy resistance. The mechanisms behind platinum resistance are not completely understood. Here, we have investigated the role of the family of p90 Ribosomal S6 kinases (RSK), important downstream mediators of ERK1/2, in the response to cisplatin chemotherapy. Strikingly, whereas treatment with cisplatin did not alter the levels of RSK1 in response to cisplatin treatment, the structurally related RSK2 protein was downregulated in an ovarian cancer cell line (A2780). Furthermore, we found that knockdown of RSK2, in contrast to knockdown of RSK1, gave rise to enhanced cisplatin sensitivity in a cisplatin sensitive as well as a cisplatin-resistant A2780 cell line. These results indicate that RSK2 is regulated in response to cisplatin treatment, and this downregulation may contribute to the cytotoxic action of cisplatin. Since RSK2 is frequently amplified in a growing number of cancers, this may have implications for the sensitivity of these tumours to platinum-based cytotoxics.
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands. m.vanjaarsveld@erasmusmc.nl
authors.forename: Marijn T M
authors.initials: MT
authors.lastname: van Jaarsveld
authors.forename: Iris C J
authors.initials: IC
authors.lastname: Blijdorp
authors.forename: Antonius W M
authors.initials: AW
authors.lastname: Boersma
authors.forename: Joris
authors.initials: J
authors.lastname: Pothof
authors.forename: Ron H J
authors.initials: RH
authors.lastname: Mathijssen
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Erik A C
authors.initials: EA
authors.lastname: Wiemer
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D002945:Cisplatin