Identifying the mechanisms involved in the survival of breast cancer cells and their ability to colonize other tissues are crucial issues for improving treatment.

The absence of the 14-3-3 protein sigma in breast cancer cells is directly associated with these cells' capacity to activate the signaling of a protein complex called Nuclear Factor-kappa B (NF-κB), which is related to tumor progression.

Scientists at the Hospital Del Mar Research Institute (IMIM; Barcelona, Spain) studied 100 patients, and analyzed the possible usefulness of determining the lack of the 14-3-3 σ and/or the activation of NF-κB in tumor cells as a factor in prognosis and diagnosis, as well as for future clinical and therapeutic applications. Many different techniques and methodologies were used in this study including, pull-down assays, immunohistochemistry, electrophoretic mobility shift assays, microarray data processing, and functional enrichment analysis of 14-3-3σ gene signatures.

They discovered that the lack of this protein does not in itself establish a prognosis factor for these types of cancer, although the NF-κB complex is an essential requirement for it to remain active chronically, as it is associated with tumor invasion and metastasis or, stated differently, the progression of the tumor. The results obtained from this project have opened up new roads of investigation that will have to center on identifying the pharmaceuticals that induce the expression of the 14-3-3 protein sigma in breast tumors and characterize their effect on tumor cells. They also hope to define which genes activated by the NF-κB complex are important for tumor progression in this group of patients and to study their potential as possible therapeutic targets.

The authors concluded that they had identified 14-3-3σ as a negative regulator of NF-κB in breast cancer and demonstrated that loss of 14-3-3 expression is directly associated with the capacity of breast cancer cells to metastasize. They consider that the current availability of high throughput sequencing technology in clinical practice, their results are of critical importance for future stratification of breast cancer patients for personalized treatments. The study was published on May 31, 2012, in the Public Library of Science One (PLoS One).

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Hospital Del Mar Research Institute