PTTG (Securin) as cancer biomarker

Abstract

Pituitary tumor transforming gene (PTTG) has originally been discovered as a gene differentially expressed between rat pituitary tumor cells and normal rat pituitary tissue. It was rapidly recognized that PTTG mRNA and protein are much more abundant in various human tumor types as compared to the corresponding non-tumor tissue. The mammalian PTTG protein was found to be a securin, required for correct sister-chromatid separation and equal distribution of mitotic chromosomes to the daughter cells. Increased levels of the protein in tumor cells result in aneuploidy and DNA instability. The potential of PTTG to initiate and support tumor development was demonstrated in xenograft models. Transgenic mice finally proved a weak oncogenic potential of the gene. PTTG exhibits a vast impact on the transcriptome of tumor cells due to its ability to bind to general transcription factors, such as SP1, and to p53, which is of major importance for cell cycle regulation and apoptosis. Among the PTTG-regulated genes are some which are associated with tumor cell migration and invasion, corresponding to the metastasis-enhancing function of PTTG observed in xenograft models. In several human tumor types, high mRNA and protein levels of PTTG have been associated with increased proliferation index, with increased risk of metastases, and – most important – with lower overall survival. Due to the similarity of results among several clinical studies, including various types of solid tumors, it can be stated that PTTG is a valuable prognostic marker in aggressive human tumor diseases.