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The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

Sernbo, Sandra LU ; Gustavsson, Elin LU ; Brennan, Donal J.; Gallagher, William M.; Rexhepaj, Elton; Rydnert, Frida LU ; Jirström, Karin LU ; Borrebaeck, Carl LU and Ek, Sara LU (2011) In BMC Cancer 11.
Abstract
Background: 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. Methods: SOX11 expression and clinicopathological data was compared using chi(2) 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... (More)
Background: 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. Methods: SOX11 expression and clinicopathological data was compared using chi(2) 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. Results: 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. Conclusions: 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
SOX11, EOC, DNA methylation, epigenetic regulation
in
BMC Cancer
volume
11
publisher
BioMed Central
external identifiers
  • wos:000295721400001
  • scopus:80053173700
ISSN
1471-2407
DOI
10.1186/1471-2407-11-405
language
English
LU publication?
yes
id
6b7e47c8-d907-4f26-bc9f-d0c031ffb18d (old id 2212924)
date added to LUP
2011-11-29 14:17:33
date last changed
2017-11-19 04:02:10
@article{6b7e47c8-d907-4f26-bc9f-d0c031ffb18d,
  abstract     = {Background: 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. Methods: SOX11 expression and clinicopathological data was compared using chi(2) 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. Results: 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. Conclusions: 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.},
  author       = {Sernbo, Sandra and Gustavsson, Elin and Brennan, Donal J. and Gallagher, William M. and Rexhepaj, Elton and Rydnert, Frida and Jirström, Karin and Borrebaeck, Carl and Ek, Sara},
  issn         = {1471-2407},
  keyword      = {SOX11,EOC,DNA methylation,epigenetic regulation},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation},
  url          = {http://dx.doi.org/10.1186/1471-2407-11-405},
  volume       = {11},
  year         = {2011},
}