PMID- 17657524
OWN - NLM
STAT- MEDLINE
DCOM- 20080417
LR  - 20181113
IS  - 0022-2631 (Print)
IS  - 0022-2631 (Linking)
VI  - 218
IP  - 1-3
DP  - 2007 Aug
TI  - Pathological significance of intracytoplasmic connexin proteins: implication in 
      tumor progression.
PG  - 73-7
AB  - A considerable amount of evidence has established that gap junctional 
      intercellular communication (GJIC) suppresses tumor development by halting the 
      stage of tumor promotion. Consistently, GJIC is downregulated in tumors. The 
      downregulation of GJIC is caused by not only the reduced expression level of 
      connexin proteins but also their aberrant cytoplasmic localization. Although it 
      has long been thought that cytoplasmic localization of connexin proteins is 
      merely one of the mechanisms of the downregulation of GJIC, careful studies with 
      human tumor samples have indicated that the expression level of intracytoplasmic 
      connexin proteins correlates well with the grade of malignancy and the 
      progression stage of tumors. Hypothesizing that intracytoplasmic connexin 
      proteins should have their proper functions and that their increase should 
      facilitate tumor progression such as cell migration, invasion and metastasis, we 
      examined the effects of overexpressed connexin32 (Cx32) protein on the phenotype 
      of human HuH7 hepatoma cells, which express a basal level of endogenous Cx32 only 
      in cytoplasm. The cells were retrovirally transduced with the Tet-off Cx32 
      construct so that withdrawal of doxycycline from the culture medium could induce 
      overexpression of Cx32 protein in cytoplasm. Even when overexpressed, Cx32 
      protein was retained in cytoplasm, i.e., Golgi apparatuses, and did not induce 
      GJIC. However, overexpression of Cx32 protein in cytoplasm enhanced both the 
      motility and the invasiveness of HuH7 cells and induced metastasis when the cells 
      were xenografted into SCID mice. Taken together, cytoplasmic accumulation of 
      connexin proteins may exert effects favorable for tumor progression.
FAU - Omori, Yasufumi
AU  - Omori Y
AD  - Department of Pathology and Immunology, Akita University School of Medicine, 
      1-1-1 Hondo, Akita, Japan. yasu@med.akita-u.ac.jp
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 - Nishimura, Takuya
AU  - Nishimura T
FAU - Enomoto, Katsuhiko
AU  - Enomoto K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20070727
PL  - United States
TA  - J Membr Biol
JT  - The Journal of membrane biology
JID - 0211301
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Connexins/*metabolism
MH  - Cytoplasm/*metabolism
MH  - Disease Progression
MH  - Gap Junctions
MH  - Humans
MH  - Neoplasms/*metabolism/pathology
RF  - 30
EDAT- 2007/07/28 09:00
MHDA- 2008/04/18 09:00
CRDT- 2007/07/28 09:00
PHST- 2007/04/30 00:00 [received]
PHST- 2007/05/14 00:00 [accepted]
PHST- 2007/07/28 09:00 [pubmed]
PHST- 2008/04/18 09:00 [medline]
PHST- 2007/07/28 09:00 [entrez]
AID - 10.1007/s00232-007-9048-6 [doi]
PST - ppublish
SO  - J Membr Biol. 2007 Aug;218(1-3):73-7. doi: 10.1007/s00232-007-9048-6. Epub 2007 
      Jul 27.