PMID- 22860069
OWN - NLM
STAT- MEDLINE
DCOM- 20130114
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 7
DP  - 2012
TI  - ARID3B induces tumor necrosis factor alpha mediated apoptosis while a novel 
      ARID3B splice form does not induce cell death.
PG  - e42159
LID - 10.1371/journal.pone.0042159 [doi]
LID - e42159
AB  - Alternative splicing is a common occurrence in many cancers. Alternative splicing 
      is linked with decreased apoptosis and chemoresistance in cancer cells. We 
      previously demonstrated that ARID3B, a member of the AT-rich interactive domain 
      (ARID) family of DNA binding proteins, is overexpressed in ovarian cancer. 
      Therefore we wanted to assess the effect of ARID3B splice forms on cell 
      viability. We identified a novel splice form of the ARID3B gene (designated as 
      ARID3B Sh), which lacks the C-terminal exons 5-9 present in the full-length 
      isoform (ARID3B Fl). ARID3B Fl is expressed in a variety of cancer cell lines. 
      Expression of ARID3B Sh varied by cell type, but was highly expressed in most 
      ovarian cancer lines. ARID3B is modestly transcriptionally activated by epidermal 
      growth factor receptor (EGFR) signaling through the PEA3 transcription factor. We 
      further found that ARID3B Fl is predominantly nuclear but is also present at the 
      plasma membrane and in the cytosol. Endogenous ARID3B Sh is present in nuclear 
      fractions, yet, when overexpressed ARID3B Sh accumulates in the cytosol and 
      membrane fractions. The differential localization of these isoforms suggests they 
      have different functions. Importantly, ARID3B Fl overexpression results in 
      upregulation of pro-apoptotic BIM and induces Tumor Necrosis Factor alpha (TNFalpha) 
      and TNF-related apoptosis inducing ligand (TRAIL) induced cell death. The ARID3B 
      Fl-induced genes include TNFalpha, TRAIL, TRADD, TNF-R2, Caspase 10 and Caspase 7. 
      Interestingly, ARID3B Sh does not induce apoptosis or expression of these genes. 
      ARID3B Fl induces death receptor mediated apoptosis while the novel splice form 
      ARID3B Sh does not induce cell death. Therefore alternative splice forms of 
      ARID3B may play different roles in ovarian cancer progression.
FAU - Joseph, Stancy
AU  - Joseph S
AD  - Department of Biochemistry and Molecular Biology, Indiana University School of 
      Medicine, South Bend, Indiana, United States of America.
FAU - Deneke, Victoria E
AU  - Deneke VE
FAU - Cowden Dahl, Karen D
AU  - Cowden Dahl KD
LA  - eng
GR  - R00 CA133190/CA/NCI NIH HHS/United States
GR  - R00CA133190/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120731
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (ARID3B protein, human)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - *Alternative Splicing
MH  - Apoptosis/*physiology
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Chromatin Immunoprecipitation
MH  - DNA Primers
MH  - DNA-Binding Proteins/genetics/metabolism/*physiology
MH  - ErbB Receptors/metabolism
MH  - Female
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Subcellular Fractions/metabolism
MH  - Tumor Necrosis Factor-alpha/*physiology
PMC - PMC3409141
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/08/04 06:00
MHDA- 2013/01/15 06:00
PMCR- 2012/07/31
CRDT- 2012/08/04 06:00
PHST- 2012/04/09 00:00 [received]
PHST- 2012/07/02 00:00 [accepted]
PHST- 2012/08/04 06:00 [entrez]
PHST- 2012/08/04 06:00 [pubmed]
PHST- 2013/01/15 06:00 [medline]
PHST- 2012/07/31 00:00 [pmc-release]
AID - PONE-D-12-10269 [pii]
AID - 10.1371/journal.pone.0042159 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(7):e42159. doi: 10.1371/journal.pone.0042159. Epub 2012 Jul 31.