The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation
<p>Abstract</p> <p>Background</p> <p>The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, m...
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| Format: | Article |
| Language: | English |
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BMC
2011-09-01
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| Series: | BMC Cancer |
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| Online Access: | http://www.biomedcentral.com/1471-2407/11/405 |
| _version_ | 1811245841390764032 |
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| author | Rexhepaj Elton Gallagher William M Brennan Donal J Gustavsson Elin Sernbo Sandra Rydnert Frida Jirström Karin Borrebaeck Carl AK Ek Sara |
| author_facet | Rexhepaj Elton Gallagher William M Brennan Donal J Gustavsson Elin Sernbo Sandra Rydnert Frida Jirström Karin Borrebaeck Carl AK Ek Sara |
| author_sort | Rexhepaj Elton |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking.</p> <p>Methods</p> <p>SOX11 expression and clinicopathological data was compared using χ<sup>2 </sup>test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation.</p> <p>Results</p> <p>SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11.</p> <p>Conclusions</p> <p>SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.</p> |
| first_indexed | 2024-04-12T14:45:22Z |
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| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T14:45:22Z |
| publishDate | 2011-09-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj.art-80020e6e060d4f09acc2ec92e5e4720d2022-12-22T03:28:41ZengBMCBMC Cancer1471-24072011-09-0111140510.1186/1471-2407-11-405The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylationRexhepaj EltonGallagher William MBrennan Donal JGustavsson ElinSernbo SandraRydnert FridaJirström KarinBorrebaeck Carl AKEk Sara<p>Abstract</p> <p>Background</p> <p>The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking.</p> <p>Methods</p> <p>SOX11 expression and clinicopathological data was compared using χ<sup>2 </sup>test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation.</p> <p>Results</p> <p>SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11.</p> <p>Conclusions</p> <p>SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.</p>http://www.biomedcentral.com/1471-2407/11/405SOX11EOCDNA methylationepigenetic regulation |
| spellingShingle | Rexhepaj Elton Gallagher William M Brennan Donal J Gustavsson Elin Sernbo Sandra Rydnert Frida Jirström Karin Borrebaeck Carl AK Ek Sara The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation BMC Cancer SOX11 EOC DNA methylation epigenetic regulation |
| title | The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation |
| title_full | The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation |
| title_fullStr | The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation |
| title_full_unstemmed | The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation |
| title_short | The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation |
| title_sort | tumour suppressor sox11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation |
| topic | SOX11 EOC DNA methylation epigenetic regulation |
| url | http://www.biomedcentral.com/1471-2407/11/405 |
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