PMID- 22007274
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20111110
LR  - 20211020
IS  - 1948-5204 (Electronic)
IS  - 1948-5204 (Print)
VI  - 3
IP  - 8
DP  - 2011 Aug 15
TI  - Intracellular chloride regulates the G(1)/S cell cycle progression in gastric 
      cancer cells.
PG  - 119-22
LID - 10.4251/wjgo.v3.i8.119 [doi]
AB  - Recent studies show that ion channels/transporters play important roles in 
      fundamental cellular functions. Several reports indicating the important roles of 
      Cl(-) channels/transporters on cell proliferation suggest that the intracellular 
      chloride concentration ([Cl(-)](i)) regulated by them would be one of critical 
      messengers. We investigated whether the [Cl(-)](i) controls cell proliferation 
      and cell cycle progression in human gastric cancer cells. Our studies indicated 
      that furosemide, a blocker of Na(+)/K(+)/2Cl(-) cotransporter (NKCC), diminished 
      cell growth by delaying the G(1)-S phase progression in gastric cancer cells with 
      high expression and activity of NKCC. Furthermore, we found that the culture in 
      the low Cl(-) medium (replacement of Cl(-) by NO(3) (-)) decreased the [Cl(-)](i) 
      and inhibited cell growth of gastric cancer cells and that this inhibition of 
      cell growth was due to cell cycle arrest at the G(0)/G(1) phase caused by 
      diminution of CDK2 and phosphorylated Rb. The culture of cells in the low Cl(-) 
      medium significantly increased expressions of p21 mRNA and protein. In addition, 
      the low Cl(-) medium induced phosphorylation of mitogen activated protein kinases 
      (MAPKs). Treatment with an inhibitor of p38 or JNK significantly suppressed p21 
      upregulation caused by culture in a low Cl(-) medium and rescued gastric cancer 
      cells from the low Cl(-)-induced G(1) cell cycle arrest. These findings revealed 
      that the [Cl(-)](i) affects the cell proliferation via activation of MAPKs 
      through upregulation of p21 in gastric cancer cells. Our results suggest that the 
      [Cl(-)](i) regulates important cellular functions in gastric cancer cells, 
      leading to the development of novel therapeutic strategies.
FAU - Shiozaki, Atsushi
AU  - Shiozaki A
AD  - Atsushi Shiozaki, Eigo Otsuji, Division of Digestive Surgery, Department of 
      Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
FAU - Otsuji, Eigo
AU  - Otsuji E
FAU - Marunaka, Yoshinori
AU  - Marunaka Y
LA  - eng
PT  - Journal Article
PL  - China
TA  - World J Gastrointest Oncol
JT  - World journal of gastrointestinal oncology
JID - 101532470
PMC - PMC3192220
OTO - NOTNLM
OT  - Cell cycle
OT  - Cell proliferation
OT  - Cl- channel
OT  - Cl- transporter
OT  - Gastric cancer
OT  - Intracellular chloride
EDAT- 2011/10/19 06:00
MHDA- 2011/10/19 06:01
PMCR- 2011/08/15
CRDT- 2011/10/19 06:00
PHST- 2011/03/31 00:00 [received]
PHST- 2011/07/25 00:00 [revised]
PHST- 2011/08/01 00:00 [accepted]
PHST- 2011/10/19 06:00 [entrez]
PHST- 2011/10/19 06:00 [pubmed]
PHST- 2011/10/19 06:01 [medline]
PHST- 2011/08/15 00:00 [pmc-release]
AID - 10.4251/wjgo.v3.i8.119 [doi]
PST - ppublish
SO  - World J Gastrointest Oncol. 2011 Aug 15;3(8):119-22. doi: 10.4251/wjgo.v3.i8.119.