PMID- 15782139
OWN - NLM
STAT- MEDLINE
DCOM- 20050630
LR  - 20231213
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 24
IP  - 22
DP  - 2005 May 19
TI  - Connexin32 as a tumor suppressor gene in a metastatic renal cell carcinoma cell 
      line.
PG  - 3684-90
AB  - Connexin genes expressing gap junction proteins have tumor-suppressive effects on 
      primary cancers with certain cell specificity, but the suppressive effects on 
      metastatic cancers are still conflicting. In this study, we show that connexin32 
      (Cx32) has a strong tumor-suppressive effect on a human metastatic renal cell 
      carcinoma cell line (Caki-1 cell). Cx32 expression in Caki-1 cells reduced in 
      vitro malignant phenotypes of the cells such as anchorage independency and 
      invasion capacity. Furthermore, the Cx32 expression drastically reduced the 
      development of Caki-1 cells in nude mice. We also determined that Cx32 reduced 
      the malignant phenotypes in Caki-1 cells mainly through the inactivation of Src 
      signaling. Especially, Cx32-dependent inactivation of Src decreased the 
      production of vascular epithelial growth factor (VEGF) via the suppression of 
      signal transducers and activators of transcription 3 (Stat3) activation, and we 
      confirmed this result using short interfering RNA. In nude mice, Cx32-transfected 
      Caki-1 cells showed lower serum level of VEGF comparing mock transfectant, and 
      the development of the cells in nude mice positively related to the VEGF level. 
      These data suggest that Cx32 acts as a tumor suppressor gene in Caki-1 cells and 
      that the tumor-suppressive effect partly depends on the inhibition of 
      Src-Stat3-VEGF signal pathway.
FAU - Fujimoto, Eriko
AU  - Fujimoto E
AD  - Department of Food Science Research for Health, National Institute of Health and 
      Nutrition, 1-23-1 Toyama, Shinjuku, 162-8636 Tokyo, Japan.
FAU - Sato, Hiromi
AU  - Sato H
FAU - Shirai, Sumiko
AU  - Shirai S
FAU - Nagashima, Yoji
AU  - Nagashima Y
FAU - Fukumoto, Keiko
AU  - Fukumoto K
FAU - Hagiwara, Hiromi
AU  - Hagiwara H
FAU - Negishi, Etsuko
AU  - Negishi E
FAU - Ueno, Koichi
AU  - Ueno K
FAU - Omori, Yasufumi
AU  - Omori Y
FAU - Yamasaki, Hiroshi
AU  - Yamasaki H
FAU - Hagiwara, Kiyokazu
AU  - Hagiwara K
FAU - Yano, Tomohiro
AU  - Yano T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Connexins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Animals
MH  - Carcinoma, Renal Cell/*genetics
MH  - Cell Line, Tumor
MH  - Connexins/*genetics
MH  - DNA-Binding Proteins/metabolism
MH  - Genes, Tumor Suppressor/*physiology
MH  - Humans
MH  - Kidney Neoplasms/*genetics
MH  - Mice
MH  - Mice, Nude
MH  - RNA, Small Interfering
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/*genetics
MH  - Trans-Activators/metabolism
MH  - Transfection
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - src-Family Kinases/metabolism
MH  - Gap Junction beta-1 Protein
EDAT- 2005/03/23 09:00
MHDA- 2005/07/01 09:00
CRDT- 2005/03/23 09:00
PHST- 2005/03/23 09:00 [pubmed]
PHST- 2005/07/01 09:00 [medline]
PHST- 2005/03/23 09:00 [entrez]
AID - 1208430 [pii]
AID - 10.1038/sj.onc.1208430 [doi]
PST - ppublish
SO  - Oncogene. 2005 May 19;24(22):3684-90. doi: 10.1038/sj.onc.1208430.