Lee, Sooyong Yoon, Seunghee Kim, Dong-Hyun 2024-01-21T01:33:44Z 2024-01-21T01:33:44Z 2021-09-05 2007-02 0090-8258 https://pubs.kist.re.kr/handle/201004/134697 Objective. The aim of this study was to elucidate the role of ERK 1/2 on cisplatin resistance in human ovarian cancer cells. Methods. The relationship between nuclear levels of ERK2 and cisplatin-induced apoptosis in human ovarian carcinoma cell line, OVCAR-3, and in cells of the cisplatin-resistant subclone, OVCAR-3/CDDP, was examined using immunoblotting and immunocytochemistry. Results. Cisplatin treatment resulted in the activation of ERK2, both in OVCAR-3 and OVCAR-3/CDDP cells. However, considerable levels of activated ERK2 existed in the nuclei of OVCAR-3/CDDP cells during serum starvation and in the early period (1-3 h) after cisplatin treatment. Conversely, phospho-ERK2 was marginally detected in the nuclei of OVCAR-3 cells prior to cisplatin treatment. These phenomena were confirmed by immunofluorescence staining of the phosphorylated ERK2 in the nuclei of both cells. High basal phospho-ERK2 in the nuclei of OVCAR-3/CDDP cells contributed to cisplatin resistance, and was supported by several observations; (1) treatment of U0126, an inhibitor of MEK/ERK signaling pathway, partially sensitized OVCAR-3/CDDP cells to cisplatin; (2) pretreatment of OVCAR-3 cells with phorbol 12-myristate 13-acetate (PMA), an activator of ERK, induced nuclear translocation of activated ERK2, which led to the suppression of cisplatin-induced apoptosis. Conclusions. These results collectively indicate that prelocalization of activated ERK2 in the nuclei contribute to cisplatin resistance in OVCAR-3/CDDP cells. (c) 2006 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE SIGNAL-REGULATED KINASE ACTIVATED PROTEIN-KINASE MAP KINASE INDUCED APOPTOSIS CARCINOMA CELLS LEUKEMIA-CELLS JURKAT CELLS INHIBITION PATHWAY CASCADE A high nuclear basal level of ERK2 phosphorylation contributes to the resistance of cisplatin-resistant human ovarian cancer cells Article 10.1016/j.ygyno.2006.08.040 1 GYNECOLOGIC ONCOLOGY, v.104, no.2, pp.338 - 344 GYNECOLOGIC ONCOLOGY 104 2 338 344 scie scopus 000244101200012 2-s2.0-33846394128 Oncology Obstetrics & Gynecology Oncology Obstetrics & Gynecology Article SIGNAL-REGULATED KINASE ACTIVATED PROTEIN-KINASE MAP KINASE INDUCED APOPTOSIS CARCINOMA CELLS LEUKEMIA-CELLS JURKAT CELLS INHIBITION PATHWAY CASCADE OVCAR-3 cells cisplatin cisplatin resistance apoptosis MAPK ERK1/2 nuclear localization