RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation
Abstract Background Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3908-y |
| _version_ | 1828354536611250176 |
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| author | Nan Wu Dong Ren Su Li Wenli Ma Shaoyan Hu Yan Jin Sheng Xiao |
| author_facet | Nan Wu Dong Ren Su Li Wenli Ma Shaoyan Hu Yan Jin Sheng Xiao |
| author_sort | Nan Wu |
| collection | DOAJ |
| description | Abstract Background Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds the switch regions of Rac1 to prevent access from GEFs. Methods Three cancer cell lines with up- or down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1 signaling and sensitivity to a group of nine chemotherapeutic drugs. RCC2 expression in lung cancer and ovarian cancer were studied using immunochemistry stain of tumor tissue arrays. Results Forced RCC2 expression in tumor cells blocked spontaneous- or Staurosporine (STS)-induced apoptosis. In contrast, RCC2 knock down in these cells resulted in increased apoptosis to STS treatment. The protective activity of RCC2 on apoptosis was revoked by a constitutively activated Rac1, confirming a role of RCC2 in apoptosis by regulating Rac1. In an immunohistochemistry evaluation of tissue microarray, RCC2 was over-expressed in 88.3% of primary lung cancer and 65.2% of ovarian cancer as compared to non-neoplastic lung and ovarian tissues, respectively. Because chemotherapeutic drugs can kill tumor cells by activating Rac1/JNK pathway, we suspect that tumors with RCC2 overexpression would be more resistant to these drugs. Tumor cells with forced RCC2 expression indeed had significant difference in drug sensitivity compared to parental cells using a panel of common chemotherapeutic drugs. Conclusions RCC2 regulates apoptosis by blocking Rac1 signaling. RCC2 expression in tumor can be a useful marker for predicting chemotherapeutic response. |
| first_indexed | 2024-04-14T02:26:20Z |
| format | Article |
| id | doaj.art-395b0a8bcc6246678444b9b47373bcbe |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-14T02:26:20Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-395b0a8bcc6246678444b9b47373bcbe2022-12-22T02:17:51ZengBMCBMC Cancer1471-24072018-01-0118111110.1186/s12885-017-3908-yRCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activationNan Wu0Dong Ren1Su Li2Wenli Ma3Shaoyan Hu4Yan Jin5Sheng Xiao6Department of Medical Genetics, Harbin Medical UniversityDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Medical Genetics, Harbin Medical UniversityDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical SchoolChildren’s Hospital of Soochow UniversityDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical SchoolAbstract Background Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds the switch regions of Rac1 to prevent access from GEFs. Methods Three cancer cell lines with up- or down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1 signaling and sensitivity to a group of nine chemotherapeutic drugs. RCC2 expression in lung cancer and ovarian cancer were studied using immunochemistry stain of tumor tissue arrays. Results Forced RCC2 expression in tumor cells blocked spontaneous- or Staurosporine (STS)-induced apoptosis. In contrast, RCC2 knock down in these cells resulted in increased apoptosis to STS treatment. The protective activity of RCC2 on apoptosis was revoked by a constitutively activated Rac1, confirming a role of RCC2 in apoptosis by regulating Rac1. In an immunohistochemistry evaluation of tissue microarray, RCC2 was over-expressed in 88.3% of primary lung cancer and 65.2% of ovarian cancer as compared to non-neoplastic lung and ovarian tissues, respectively. Because chemotherapeutic drugs can kill tumor cells by activating Rac1/JNK pathway, we suspect that tumors with RCC2 overexpression would be more resistant to these drugs. Tumor cells with forced RCC2 expression indeed had significant difference in drug sensitivity compared to parental cells using a panel of common chemotherapeutic drugs. Conclusions RCC2 regulates apoptosis by blocking Rac1 signaling. RCC2 expression in tumor can be a useful marker for predicting chemotherapeutic response.http://link.springer.com/article/10.1186/s12885-017-3908-yRCC2Rac1Apoptosis |
| spellingShingle | Nan Wu Dong Ren Su Li Wenli Ma Shaoyan Hu Yan Jin Sheng Xiao RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation BMC Cancer RCC2 Rac1 Apoptosis |
| title | RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation |
| title_full | RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation |
| title_fullStr | RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation |
| title_full_unstemmed | RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation |
| title_short | RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by regulating Rac1 activation |
| title_sort | rcc2 over expression in tumor cells alters apoptosis and drug sensitivity by regulating rac1 activation |
| topic | RCC2 Rac1 Apoptosis |
| url | http://link.springer.com/article/10.1186/s12885-017-3908-y |
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