Downregulation of survivin is associated with reductions in TNF receptors' mRNA and protein and alterations in nuclear factor kappa B signaling in urothelial cancer cells.

Because survivin is selectively expressed in and associated with an unfavorable prognosis in transitional cell carcinoma of the bladder (TCC), we treated T-24 cells with survivin siRNA. Survivin siRNA treatment caused a profound decrease of survivin protein that was associated with decreased cell growth, a specific G2/M arrest and increased cytochrome c release. Microarray analysis of apoptosis genes showed that levels of 14/114 gene products were decreased after 72 hours treatment with survivin siRNA, including survivin, three TNF receptors, Akt, c-Abl, caspases and their related genes and Bcl-2 and NF-kappaB signaling related genes. TNFR1, pro-caspase-2 and Akt protein levels were decreased after survivin siRNA treatment for 48 and 72 hours. Downregulation of survivin causes changes in mitosis and apoptosis, which may be related to changes in TNF receptors and NF-kappaB signaling.