Expression of 14-3-3σ in cervical squamous cell carcinomas: Relationship with clinical outcome

Abstract

Abstract. 14-3-3 sigma (Û) sequesters the cdc2-cyclin B1 complex in the cytoplasm resulting in G2 arrest. Inactivation and reduced expression of 14-3-3Û have been reported in a varity of cancers. In the present study, we investigated the expression of 14-3-3Û in a series of 297 cervical squamous cell carcinoma (SCC) to clarify the prognostic value. Using immunohistochemical methods we found high levels of 14-3-3Û 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 14-3-3Û mRNA measured by reverse-transcription polymerase chain reaction (RT-PCR) and 14-3-3Û protein were not significant associated. 14-3-3Û expression in cytoplasm, nuclear and cytoplasm/nuclear were not significantly correlated to disease-specific survival or disease-free survival. In conclusion, reduced expression of 14-3-3Û protein in the cytoplasm and shuttle of 14-3-3Û protein into the nucleus in a relatively high number of cases indicate that 14-3-3Û may be important in the carcinogenesis of cervical SCCs by two different mechanisms; reduction and nuclear translocation of 14-3-3Û protein. Furthermore, the non-significant correlation between expression levels of 14-3-3Û mRNA and protein support a post-transcriptional regulation in cervical SCCs. The protein has no prognostic value in cervical cancers.

Expression of 14‐3‐3 sigma and eta proteins is unrelated to survival in metastatic high‐grade serous carcinoma

“…The clinical relevance of 14‐3‐3 proteins appears to depend on the organ of origin and histology, and the majority of studies assessing this issue have focused on 14‐3‐3σ protein. Previous analyses of gynecologic carcinomas showed association between loss of 14‐3‐3σ protein expression and poor prognosis in endometrial carcinoma, but no clinical relevance in cervical or vulvar squamous cell carcinoma .…”

14-3-3σ expression is associated with poor pathological complete response to neoadjuvant chemotherapy in human breast cancers

“…However, contradictory results have also been reported, namely, that there is no association between 14-3-3r promoter hypermethylation and negative 14-3-3r expression [6] in breast cancers, and that no correlation exists between 14-3-3r protein expression and 14-3-3r mRNA expression in uterine cervical cancers and colorectal cancers [15,18]. These results seem to indicate that the role of 14-3-3r promoter hypermethylation in silencing of the 14-3-3r gene remains controversial.…”

Comparison of immunoreaction between two commercial antibodies against 14-3-3σprotein in canine tissues

“…14-3-3σ is a protein kinase-dependent activator tyrosine and endogenous inhibitor of protein kinase C; it plays a negative role in the G2/M checkpoint, pausing the cell cycle and allowing DNA repair. Loss of 14-3-3σ expression results in malignant transformation in vitro and supports tumour formation in vivo, which suggests its role as a tumour suppressor gene (Holm et al 2009). Several studies in both human and canine species have used immunohistochemical techniques to detect 14-3-3σ, especially in neoplastic diseases.…”

“…Several studies in both human and canine species have used immunohistochemical techniques to detect 14-3-3σ, especially in neoplastic diseases. However, the immunohistochemical procedures and the antibodies employed in each work vary greatly between authors (Nakajima et al 2003;Holm et al 2009). In veterinary science, it has been recently investigated the expression of σ isoform in normal and neoplastic canine tissues, showing that this protein is an epithelial cell marker and that its expression is altered in canine tumours (Suárez-Bonnet et al 2010.…”

“…In veterinary science, it has been recently investigated the expression of σ isoform in normal and neoplastic canine tissues, showing that this protein is an epithelial cell marker and that its expression is altered in canine tumours (Suárez-Bonnet et al 2010. Since polyclonal and monoclonal antibodies have different sensitivity and specificity to detect a given antigen (Holm et al 2009), and the 14-3-3 family has at least seven isoforms, it would be of interest to study the expression of σ isoform using different antibodies in the same tissues.…”