E74-like factor 2 regulates valosin-containing protein expression.
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.
Zhang
Binglin
B
Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Tomita
Yasuhiko
Y
Qiu
Ying
Y
He
Juxiang
J
Morii
Eiichi
E
Noguchi
Shinzaburo
S
Aozasa
Katsuyuki
K
D024506:5' Flanking Region / Q000502:physiology; D000251:Adenosine Triphosphatases / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D034622:RNA Interference; D016415:Sequence Alignment; D014157:Transcription Factors / Q000502:physiology*; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D014157:Transcription Factors; C101003:ELF2 protein, human; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse