Stannin (Snn) is a highly conserved, vertebrate protein whose cellular function is unclear. We have recently demonstrated in human umbilical vein endothelial cells (HUVECs) that Snn gene expression is significantly induced by tumor necrosis factor-α (TNF-α) in a protein kinase C- (PKC-)-dependent manner. In HUVEC, TNF-α stimulation of HUVECs results in altered gene expression, and a slowing or halting of cell growth. An initial set of experiments established that Snn knockdown via siRNA, prior to TNF-α treatment, resulted in a significant inhibition of HUVEC growth compared to TNF-α treatment alone. In order to assess how Snn may be involved in TNF-α signaling in HUVEC growth arrest, we performed microarray analysis of TNF-α-stimulated HUVECs with and without Snn knockdown via siRNA. The primary comparison made was between TNF-α-stimulated HUVECs and TNF-α-exposed HUVECs that had Snn knocked down via Snn-specific siRNAs. Ninety-six genes were differentially expressed between these two conditions. Of particular interest was the significant upregulation of several genes associated with control of cell growth and/or the cell cycle, including interleukin-4, p29, WT1/PRKC, HRas-like suppressor, and MDM4. These genes act upon cyclin D1 and/or p53, both of which are key regulators of the G1 phase of the cell cycle. Functional studies further supported the role of Snn in cell growth, as cell cycle analysis using flow cytometry shows a significant increase of G1 cell cycle arrest in HUVECs with Snn knockdown in response to TNF-α treatment. Together these studies suggest a functional role of Snn in regulation of TNF-α-induced signaling associated with HUVEC growth arrest.
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Document Type: Review Article
Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA
Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA, Jake Gittlen Cancer Research Institute, Penn State College of Medicine, Hershey, PA 17033, USA
Publication date: January 1, 2006
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Gene Expression, The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression, The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.