Small interfering RNA against PTTG: a novel therapy for ovarian cancer.
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 down-regulation 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.
El-Naggar
Shahenda M
SM
Department of Medicine, and the James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Malik
Mohammed T
MT
Kakar
Sham S
SS
D000818:Animals; D002277:Carcinoma / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000628:therapy*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000235:genetics*; D064249:Securin; D014162:Transfection
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human