E74-like factor 2 regulates valosin-containing protein expression
- Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871 (Japan)
- Department of Pathology, Medical School of Tongji University, Shanghai (China)
- Department of Surgical Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan)
Enhanced expression of valosin-containing protein (VCP) correlates with invasion and metastasis of cancers. To clarify the transcription mechanism of VCP, human and mouse genomic sequence was compared, revealing a 260 bp DNA sequence in the 5'-flanking region of VCP gene to be highly conserved between the two, in which binding motif of E74-like factor 2/new Ets-related factor (ELF2/NERF) was identified. Chromatin immunoprecipitation assay showed binding of ELF2/NERF to the 5'-flanking region of VCP gene. Knock-down of ELF2/NERF by siRNA decreased expression level of VCP. Viability of cells under tumor necrosis factor-alpha treatment significantly reduced in ELF2/NERF-knock-down breast cancer cell line. Immunohistochemical analysis on clinical breast cancer specimens showed a correlation of nuclear ELF2/NERF expression with VCP expression and proliferative activity of cells shown by Ki-67 immunohistochemistry. These findings indicate that ELF2/NERF promotes VCP transcription and that ELF2/NERF-VCP pathway might be important for cell survival and proliferation under cytokine stress.
- OSTI ID:
- 20991330
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 356, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2007.02.160; PII: S0006-291X(07)00456-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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