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Expression of 14-3-3sigma in cervical squamous cell carcinomas: relationship with clinical outcome
Ruth Holm1, Tayeba Ali, Debbie H Svendsrud
1Division of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. ruth.holm@radiumhospitalet.no
Abstract:
14-3-3 sigma (sigma) sequesters the cdc2-cyclin B1 complex in the cytoplasm resulting in G2 arrest. Inactivation and reduced expression of 14-3-3sigma have been reported in a varity of cancers. In the present study, we investigated the expression of 14-3-3sigma in a series of 297 cervical squamous cell carcinoma (SCC) to clarify the prognostic value. Using immunohistochemical methods we found high levels of 14-3-3sigma protein in cytoplasm of 143 (48.1%), in nucleus of 113 (38.0%) and in both cytoplasm and nucleus of 147 (49.5%) cases, whereas, low levels were present in cytoplasm of 154 (51.9%), in nucleus of 184 (62.0%) and in both cytoplasm and nucleus of 150 (50.5%) cases. Levels of 14-3-3sigma mRNA measured by reverse-transcription polymerase chain reaction (RT-PCR) and 14-3-3sigma protein were not significant associated. 14-3-3sigma expression in cytoplasm, nuclear and cytoplasm/nuclear were not significantly correlated to disease-specific survival or disease-free survival. In conclusion, reduced expression of 14-3-3sigma protein in the cytoplasm and shuttle of 14-3-3sigma protein into the nucleus in a relatively high number of cases indicate that 14-3-3sigma may be important in the carcinogenesis of cervical SCCs by two different mechanisms; reduction and nuclear translocation of 14-3-3sigma protein. Furthermore, the non-significant correlation between expression levels of 14-3-3sigma mRNA and protein support a post-transcriptional regulation in cervical SCCs. The protein has no prognostic value in cervical cancers.
Insights
Reduced 14-3-3 sigma expression in cervical cancer cytoplasm and nuclear translocation suggest roles in carcinogenesis. However, 14-3-3 sigma protein levels do not predict patient prognosis in cervical squamous cell carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Cell Cycle Regulation
Background:
- 14-3-3 sigma protein regulates cell cycle arrest by sequestering the cdc2-cyclin B1 complex.
- Inactivation and reduced expression of 14-3-3 sigma are observed in various cancers.
- The role of 14-3-3 sigma in cervical cancer development and prognosis requires further investigation.
Purpose of the Study:
- To investigate the expression patterns of 14-3-3 sigma in cervical squamous cell carcinoma (SCC).
- To determine the prognostic value of 14-3-3 sigma expression in cervical SCC.
- To explore the relationship between 14-3-3 sigma mRNA and protein levels and their regulation.
Main Methods:
- Immunohistochemistry was used to assess 14-3-3 sigma protein expression in the cytoplasm and nucleus of 297 cervical SCC samples.
- Reverse-transcription polymerase chain reaction (RT-PCR) was employed to measure 14-3-3 sigma mRNA levels.
- Statistical analyses were performed to correlate protein expression with survival outcomes.
Main Results:
- High and low levels of 14-3-3 sigma protein were detected in the cytoplasm, nucleus, and both compartments in a significant portion of cervical SCC cases.
- No significant association was found between 14-3-3 sigma mRNA and protein levels.
- 14-3-3 sigma expression levels in the cytoplasm, nucleus, or both were not significantly correlated with disease-specific survival or disease-free survival.
Conclusions:
- Reduced cytoplasmic 14-3-3 sigma and nuclear translocation may indicate its involvement in cervical SCC carcinogenesis through distinct mechanisms.
- The lack of correlation between mRNA and protein levels suggests post-transcriptional regulation of 14-3-3 sigma in cervical SCC.
- 14-3-3 sigma protein expression does not serve as a prognostic marker for cervical cancer.