PMID- 20209499
OWN - NLM
STAT- MEDLINE
DCOM- 20101230
LR  - 20231213
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 128
IP  - 1
DP  - 2011 Jan 1
TI  - Cytoplasmic accumulation of connexin32 expands cancer stem cell population in 
      human HuH7 hepatoma cells by enhancing its self-renewal.
PG  - 51-62
LID - 10.1002/ijc.25308 [doi]
AB  - Although the connexin32 (Cx32)-mediated gap junction is abolished in 
      hepatocellular carcinoma (HCC), the expression of cytoplasmic Cx32 tends to 
      increase in correspondence with the grade of malignancy. Establishing a Tet-off 
      expression system in human nonmetastatic HuH7 HCC cells where cytoplasmic Cx32 
      was overexpressed by doxycycline (Dox) withdrawal, we previously demonstrated 
      that overexpression of cytoplasmic Cx32 made HuH7 cells metastatic in mice. In 
      our study, hypothesizing that the cytoplasmic Cx32-induced metastasis may involve 
      expansion of the cancer stem cell (CSC) population, we examined whether 
      cytoplasmic Cx32 controlled the size of the side population (SP) in HuH7 Tet-off 
      Cx32 cells. Fluorescence-activated cell sorting revealed that SP was expanded in 
      a Dox-free medium compared with a Dox-supplemented one. Although cytoplasmic Cx32 
      did not block maturation from SP to non-SP, purified SP reconstituted a larger SP 
      fraction in the Dox-free medium than in the Dox-supplemented one. Furthermore, 
      although SP from HuH7 Tet-off mock cells formed a similar number of CSC spheres 
      of a similar size whether with or without Dox, SP from HuH7 Tet-off Cx32 cells 
      developed a greater number of larger CSC spheres in the Dox-free medium than in 
      the Dox-supplemented one. Taken together, these results suggest that accumulation 
      of cytoplasmic Cx32 should enhance self-renewal of CSC to expand the CSC 
      population in HCC.
CI  - Copyright (c) 2010 UICC.
FAU - Kawasaki, Yohei
AU  - Kawasaki Y
AD  - Department of Molecular and Tumour Pathology, Akita University Graduate School of 
      Medicine, Akita, Japan.
FAU - Omori, Yasufumi
AU  - Omori Y
FAU - Li, Qingchang
AU  - Li Q
FAU - Nishikawa, Yuji
AU  - Nishikawa Y
FAU - Yoshioka, Toshiaki
AU  - Yoshioka T
FAU - Yoshida, Masayuki
AU  - Yoshida M
FAU - Ishikawa, Kazuo
AU  - Ishikawa K
FAU - Enomoto, Katsuhiko
AU  - Enomoto K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Connexins)
RN  - F8VB5M810T (Tetracycline)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Carcinoma, Hepatocellular/genetics/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - *Cell Proliferation
MH  - Connexins/genetics/*metabolism
MH  - Cytoplasm/drug effects/metabolism
MH  - Doxycycline/pharmacology
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique, Indirect
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Immunoblotting
MH  - Liver Neoplasms, Experimental/genetics/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Metastasis
MH  - Neoplastic Stem Cells/*metabolism/pathology
MH  - Tetracycline/pharmacology
MH  - Transplantation, Heterologous
MH  - Gap Junction beta-1 Protein
EDAT- 2010/03/09 06:00
MHDA- 2010/12/31 06:00
CRDT- 2010/03/09 06:00
PHST- 2010/03/09 06:00 [entrez]
PHST- 2010/03/09 06:00 [pubmed]
PHST- 2010/12/31 06:00 [medline]
AID - 10.1002/ijc.25308 [doi]
PST - ppublish
SO  - Int J Cancer. 2011 Jan 1;128(1):51-62. doi: 10.1002/ijc.25308.