Background: Pituitary tumor transforming gene1 (PTTG1) is a novel oncogene that is expressed in most tumors. It encodes a protein that is primarily involved in the regulation of sister chromatid separation during cell division. The oncogenic potential of PTTG1 has been well characterized in the mouse, particularly mouse fibroblast (NIH3T3) cells, in which it induces cell proliferation, promotes tumor formation and angiogenesis. Human tumorigenesis is a complex and a multistep process often requiring concordant expression of a number of genes. Also due to differences between rodent and human cell biology it is difficult to extrapolate results from mouse models to humans. To determine if PTTG1 functions similarly as an oncogene in humans, we have characterized its effects on human embryonic kidney (HEK293) cells.

Abstract. Ovarian epithelial cancer is a significant cause of death among women, accounting for 5% of all female cancer-related fatalities. A lack of reliable detection methods and resistance to chemotherapy agents are considerable obstacles in the treatment of this cancer. Recently, high-level expression of the pituitary tumor transforming gene (PTTG) was found in a wide range of tumors, including ovarian cancers. Elevated PTTG levels were found to induce cellular transformation in vitro and tumor formation in nude mice. Therefore, we hypothesize a correlation exists between the levels of PTTG expression and tumorigenesis, and that downregulation of PTTG levels will result in the suppression of tumor growth. We used small interfering RNA (siRNA) to silence PTTG expression in human A2780 ovarian carcinoma cells and assessed the effect of PTTG silencing in tumor formation in vitro and in vivo. The siRNA directed against PTTG reduced its expression at both the mRNA and protein levels. A fifty percent reduction in cell proliferation was achieved in cells constitutively expressing PTTG siRNA compared to vector or control-siRNA transfected cells. Furthermore, colony formation in soft agar was reduced by 70% in PTTG siRNA stable cell lines. Using nude mice, we showed that animals injected with A2780 cells constitutively expressing PTTG-siRNA decreased the incidence of tumor development and tumor growth. Taken together, these results strongly suggest that PTTG may serve as an important molecular target for the discovery of new anticancer agents and treatment strategies.

No abstract

No abstract