PMID- 24867691
OWN - NLM
STAT- MEDLINE
DCOM- 20141106
LR  - 20211021
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 111
IP  - 1
DP  - 2014 Jul 8
TI  - Connexins and cyclooxygenase-2 crosstalk in the expression of radiation-induced 
      bystander effects.
PG  - 125-31
LID - 10.1038/bjc.2014.276 [doi]
AB  - BACKGROUND: Signalling events mediated by connexins and cyclooxygenase-2 (COX-2) 
      have important roles in bystander effects induced by ionising radiation. However, 
      whether these proteins mediate bystander effects independently or cooperatively 
      has not been investigated. METHODS: Bystander normal human fibroblasts were 
      cocultured with irradiated adenocarcinoma HeLa cells in which specific connexins 
      (Cx) are expressed in the absence of endogenous Cx, before and after COX-2 
      knockdown, to investigate DNA damage in bystander cells and their progeny. 
      RESULTS: Inducible expression of gap junctions composed of connexin26 (Cx26) in 
      irradiated HeLa cells enhanced the induction of micronuclei in bystander cells 
      (P<0.01) and reduced the coculture time necessary for manifestation of the 
      effect. In contrast, expression of connexin32 (Cx32) conferred protective 
      effects. COX-2 knockdown in irradiated HeLa Cx26 cells attenuated the bystander 
      response due to connexin expression. However, COX-2 knockdown resulted in 
      enhanced micronucleus formation in the progeny of the bystander cells (P<0.001). 
      COX-2 knockdown delayed junctional communication in HeLa Cx26 cells, and reduced, 
      in the plasma membrane, the physical interaction of Cx26 with MAPKKK, a 
      controller of the MAPK pathway that regulates COX-2 and connexin. CONCLUSIONS: 
      Junctional communication and COX-2 cooperatively mediate the propagation of 
      radiation-induced non-targeted effects. Characterising the mediating events 
      affected by both mechanisms may lead to new approaches that mitigate secondary 
      debilitating effects of cancer radiotherapy.
FAU - Zhao, Y
AU  - Zhao Y
AD  - Department of Radiology, Rutgers University, New Jersey Medical School, Cancer 
      Center, Newark, NJ 07103, USA.
FAU - de Toledo, S M
AU  - de Toledo SM
AD  - Department of Radiology, Rutgers University, New Jersey Medical School, Cancer 
      Center, Newark, NJ 07103, USA.
FAU - Hu, G
AU  - Hu G
AD  - Department of Radiology, Rutgers University, New Jersey Medical School, Cancer 
      Center, Newark, NJ 07103, USA.
FAU - Hei, T K
AU  - Hei TK
AD  - Center for Radiological Research, Department of Radiation Oncology, Columbia 
      University Medical Center, New York, NY 10032, USA.
FAU - Azzam, E I
AU  - Azzam EI
AD  - Department of Radiology, Rutgers University, New Jersey Medical School, Cancer 
      Center, Newark, NJ 07103, USA.
LA  - eng
GR  - P01 CA049062/CA/NCI NIH HHS/United States
GR  - CA049062/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140527
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Connexins)
RN  - 0 (GJB2 protein, human)
RN  - 127120-53-0 (Connexin 26)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
SB  - IM
MH  - Bystander Effect/*radiation effects
MH  - Coculture Techniques
MH  - Connexin 26
MH  - Connexins/*metabolism
MH  - Cyclooxygenase 2/*metabolism
MH  - Fibroblasts/cytology/metabolism/radiation effects
MH  - Gap Junctions/metabolism/radiation effects
MH  - HeLa Cells
MH  - Humans
PMC - PMC4090739
EDAT- 2014/05/29 06:00
MHDA- 2014/11/07 06:00
PMCR- 2015/07/01
CRDT- 2014/05/29 06:00
PHST- 2013/12/31 00:00 [received]
PHST- 2014/03/24 00:00 [revised]
PHST- 2014/04/25 00:00 [accepted]
PHST- 2014/05/29 06:00 [entrez]
PHST- 2014/05/29 06:00 [pubmed]
PHST- 2014/11/07 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - bjc2014276 [pii]
AID - 10.1038/bjc.2014.276 [doi]
PST - ppublish
SO  - Br J Cancer. 2014 Jul 8;111(1):125-31. doi: 10.1038/bjc.2014.276. Epub 2014 May 
      27.