RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy.
Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical ca...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3602518?pdf=render |
| _version_ | 1828722507016830976 |
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| author | Olga Martinho Filipe Pinto Sara Granja Vera Miranda-Gonçalves Marise A R Moreira Luis F J Ribeiro Celso di Loreto Marsha R Rosner Adhemar Longatto-Filho Rui Manuel Reis |
| author_facet | Olga Martinho Filipe Pinto Sara Granja Vera Miranda-Gonçalves Marise A R Moreira Luis F J Ribeiro Celso di Loreto Marsha R Rosner Adhemar Longatto-Filho Rui Manuel Reis |
| author_sort | Olga Martinho |
| collection | DOAJ |
| description | Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135), and expressed at low levels in the cervix invasive carcinomas (∼15% (19/124). Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer. |
| first_indexed | 2024-04-12T05:41:39Z |
| format | Article |
| id | doaj.art-08d00b241ec9471a95a9fcefcad822fb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T05:41:39Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-08d00b241ec9471a95a9fcefcad822fb2022-12-22T03:45:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5910410.1371/journal.pone.0059104RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy.Olga MartinhoFilipe PintoSara GranjaVera Miranda-GonçalvesMarise A R MoreiraLuis F J RibeiroCelso di LoretoMarsha R RosnerAdhemar Longatto-FilhoRui Manuel ReisCervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135), and expressed at low levels in the cervix invasive carcinomas (∼15% (19/124). Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer.http://europepmc.org/articles/PMC3602518?pdf=render |
| spellingShingle | Olga Martinho Filipe Pinto Sara Granja Vera Miranda-Gonçalves Marise A R Moreira Luis F J Ribeiro Celso di Loreto Marsha R Rosner Adhemar Longatto-Filho Rui Manuel Reis RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy. PLoS ONE |
| title | RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy. |
| title_full | RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy. |
| title_fullStr | RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy. |
| title_full_unstemmed | RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy. |
| title_short | RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy. |
| title_sort | rkip inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy |
| url | http://europepmc.org/articles/PMC3602518?pdf=render |
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