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c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma
In this study, we investigated the therapeutic effects of c-MET inhibition in ovarian clear cell carcinoma (OCCC). Expression levels of c-MET in the epithelial ovarian cancers (EOCs) and normal ovarian tissues were evaluated using real-time PCR. To test the effects of c-MET inhibitors in OCCC cell l...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137074/ https://www.ncbi.nlm.nih.gov/pubmed/27917934 http://dx.doi.org/10.1038/srep38502 |
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author | Kim, Ha-Jeong Yoon, Aera Ryu, Ji-Yoon Cho, Young-Jae Choi, Jung-Joo Song, Sang Yong Bang, Heejin Lee, Ji Soo Cho, William Chi Choi, Chel Hun Lee, Jeong-Won Kim, Byoung-Gie Bae, Duk-Soo |
author_facet | Kim, Ha-Jeong Yoon, Aera Ryu, Ji-Yoon Cho, Young-Jae Choi, Jung-Joo Song, Sang Yong Bang, Heejin Lee, Ji Soo Cho, William Chi Choi, Chel Hun Lee, Jeong-Won Kim, Byoung-Gie Bae, Duk-Soo |
author_sort | Kim, Ha-Jeong |
collection | PubMed |
description | In this study, we investigated the therapeutic effects of c-MET inhibition in ovarian clear cell carcinoma (OCCC). Expression levels of c-MET in the epithelial ovarian cancers (EOCs) and normal ovarian tissues were evaluated using real-time PCR. To test the effects of c-MET inhibitors in OCCC cell lines, we performed MTT and apoptosis assays. We used Western blots to evaluate the expression of c-MET and its down-stream pathway. In vivo experiments were performed to test the effects of c-MET inhibitor on tumor growth in orthotopic mouse xenografts of OCCC cell line RMG1 and a patient-derived tumor xenograft (PDX) model of OCCC. c-MET expression was significantly greater in OCCCs compared with serous carcinomas and normal ovarian tissues (p < 0.001). In in vitro study, inhibition of c-MET using c-MET inhibitors (SU11274 or crizotinib) significantly decreased the proliferation, and increased the apoptosis of OCCC cells. SU11274 decreased expression of the p-c-MET proteins and blocked the phosphorylation of down-stream proteins Akt and Erk. Furthermore, SU11274 treatment significantly decreased the in vivo tumor weight in xenograft models of RMG1 cell and a PDX model for OCCC compared to control (p = 0.004 and p = 0.009, respectively). |
format | Online Article Text |
id | pubmed-5137074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51370742017-01-27 c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma Kim, Ha-Jeong Yoon, Aera Ryu, Ji-Yoon Cho, Young-Jae Choi, Jung-Joo Song, Sang Yong Bang, Heejin Lee, Ji Soo Cho, William Chi Choi, Chel Hun Lee, Jeong-Won Kim, Byoung-Gie Bae, Duk-Soo Sci Rep Article In this study, we investigated the therapeutic effects of c-MET inhibition in ovarian clear cell carcinoma (OCCC). Expression levels of c-MET in the epithelial ovarian cancers (EOCs) and normal ovarian tissues were evaluated using real-time PCR. To test the effects of c-MET inhibitors in OCCC cell lines, we performed MTT and apoptosis assays. We used Western blots to evaluate the expression of c-MET and its down-stream pathway. In vivo experiments were performed to test the effects of c-MET inhibitor on tumor growth in orthotopic mouse xenografts of OCCC cell line RMG1 and a patient-derived tumor xenograft (PDX) model of OCCC. c-MET expression was significantly greater in OCCCs compared with serous carcinomas and normal ovarian tissues (p < 0.001). In in vitro study, inhibition of c-MET using c-MET inhibitors (SU11274 or crizotinib) significantly decreased the proliferation, and increased the apoptosis of OCCC cells. SU11274 decreased expression of the p-c-MET proteins and blocked the phosphorylation of down-stream proteins Akt and Erk. Furthermore, SU11274 treatment significantly decreased the in vivo tumor weight in xenograft models of RMG1 cell and a PDX model for OCCC compared to control (p = 0.004 and p = 0.009, respectively). Nature Publishing Group 2016-12-05 /pmc/articles/PMC5137074/ /pubmed/27917934 http://dx.doi.org/10.1038/srep38502 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Kim, Ha-Jeong Yoon, Aera Ryu, Ji-Yoon Cho, Young-Jae Choi, Jung-Joo Song, Sang Yong Bang, Heejin Lee, Ji Soo Cho, William Chi Choi, Chel Hun Lee, Jeong-Won Kim, Byoung-Gie Bae, Duk-Soo c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma |
title | c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma |
title_full | c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma |
title_fullStr | c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma |
title_full_unstemmed | c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma |
title_short | c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma |
title_sort | c-met as a potential therapeutic target in ovarian clear cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137074/ https://www.ncbi.nlm.nih.gov/pubmed/27917934 http://dx.doi.org/10.1038/srep38502 |
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