Elucidation of stannin function using microarray analysis

Implications for cell cycle control

Brian E. Reese, Dan Krissinger, Jong Yun, Melvin Billingsley

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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-ε (PKC-ε)-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.

Original languageEnglish (US)
Pages (from-to)41-52
Number of pages12
JournalGene Expression
Volume13
Issue number1
DOIs
StatePublished - Dec 1 2005

Fingerprint

Human Umbilical Vein Endothelial Cells
Microarray Analysis
Cell Cycle Checkpoints
Tumor Necrosis Factor-alpha
Growth
Cell Cycle
Small Interfering RNA
stannin
Genes
G1 Phase Cell Cycle Checkpoints
Gene Expression
Cyclin D1
G1 Phase
Interleukin-4
Protein Kinase C
Vertebrates
Flow Cytometry
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics

Cite this

Reese, Brian E. ; Krissinger, Dan ; Yun, Jong ; Billingsley, Melvin. / Elucidation of stannin function using microarray analysis : Implications for cell cycle control. In: Gene Expression. 2005 ; Vol. 13, No. 1. pp. 41-52.
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Elucidation of stannin function using microarray analysis : Implications for cell cycle control. / Reese, Brian E.; Krissinger, Dan; Yun, Jong; Billingsley, Melvin.

In: Gene Expression, Vol. 13, No. 1, 01.12.2005, p. 41-52.

Research output: Contribution to journalArticle

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