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

Bayan T Takizawa; Edward M Uchio; Justin J Cohen; Marcia A Wheeler; Robert M Weiss

doi:10.1080/07357900701600954

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

Cancer Invest. 2007 Dec;25(8):678-84. doi: 10.1080/07357900701600954.

Authors

Bayan T Takizawa¹, Edward M Uchio, Justin J Cohen, Marcia A Wheeler, Robert M Weiss

Affiliation

¹ Yale University School of Medicine, Section of Urology, New Haven, Connecticut 06520-8041, USA.

PMID: 18058462
DOI: 10.1080/07357900701600954

Abstract

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.

MeSH terms

Apoptosis
Caffeic Acids / pharmacology
Cell Line, Tumor
Chromones / pharmacology
Humans
Inhibitor of Apoptosis Proteins
Microtubule-Associated Proteins / genetics*
Microtubule-Associated Proteins / metabolism
Morpholines / pharmacology
NF-kappa B / physiology*
Neoplasm Proteins / genetics*
Neoplasm Proteins / metabolism
Phenylethyl Alcohol / analogs & derivatives
Phenylethyl Alcohol / pharmacology
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
RNA, Messenger / analysis
RNA, Small Interfering / genetics
Receptors, Tumor Necrosis Factor, Type I / analysis
Receptors, Tumor Necrosis Factor, Type I / genetics*
Signal Transduction*
Survivin
Transfection
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / metabolism*

Substances

BIRC5 protein, human
Caffeic Acids
Chromones
Inhibitor of Apoptosis Proteins
Microtubule-Associated Proteins
Morpholines
NF-kappa B
Neoplasm Proteins
RNA, Messenger
RNA, Small Interfering
Receptors, Tumor Necrosis Factor, Type I
Survivin
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Proto-Oncogene Proteins c-akt
caffeic acid phenethyl ester
Phenylethyl Alcohol