PMID- 11464280
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 20
IP  - 31
DP  - 2001 Jul 12
TI  - Connexin43 suppresses proliferation of osteosarcoma U2OS cells through 
      post-transcriptional regulation of p27.
PG  - 4138-49
AB  - Many lines of evidence indicate that connexin genes expressing gap junction (GJ) 
      proteins inhibit tumor cell proliferation. However, the precise molecular 
      mechanisms remain unclear. In this study, we show that overexpression of 
      connexin43 (Cx43) suppressed proliferation of human osteosarcoma U2OS cells 
      through inhibition of the cell cycle transition from G1 to S phase. This 
      inhibition was attributed to a significant accumulation of the hypophosphorylated 
      retinoblastoma (Rb) protein, which was causally related to decreases in the 
      kinase activities of cyclin-dependent kinases (CDKs) 2 and 4. Enforced Cx43 
      expression markedly increased the level of the CDK inhibitor p27. This increase 
      resulted from an increased synthesis and a reduced degradation of the p27 
      proteins, but not influence of the p27 mRNA. Moreover, we show that the 
      Cx43-modulated GJ function was the main contributor to the elevation in p27 
      levels, in which cAMP was involved. These data suggest that Cx43 appears to 
      inhibit proliferation of U2OS cells by increasing the levels of p27 proteins via 
      post-transcriptional regulatory mechanisms.
FAU - Zhang, Y W
AU  - Zhang YW
AD  - Department of Cellular Physiological Chemistry, Tokyo Medical and Dental 
      University, 1-5-45 Yushima, Bunkyo-Ku, 113-8549 Tokyo Japan.
FAU - Morita, I
AU  - Morita I
FAU - Ikeda, M
AU  - Ikeda M
FAU - Ma, K W
AU  - Ma KW
FAU - Murota, S
AU  - Murota S
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Connexin 43)
RN  - 0 (DNA Primers)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDC2-CDC28 Kinases)
RN  - EC 2.7.11.22 (CDK2 protein, human)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Base Sequence
MH  - Bone Neoplasms/metabolism/*pathology
MH  - *CDC2-CDC28 Kinases
MH  - Cell Communication/physiology
MH  - Cell Division/*physiology
MH  - Connexin 43/*physiology
MH  - Cyclin-Dependent Kinase 2
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinases/metabolism
MH  - DNA Primers
MH  - Gap Junctions/physiology
MH  - Humans
MH  - Osteosarcoma/metabolism/*pathology
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - *Proto-Oncogene Proteins
MH  - *RNA Processing, Post-Transcriptional
MH  - Retinoblastoma Protein/metabolism
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 2001/07/21 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/07/21 10:00
PHST- 2001/03/05 00:00 [received]
PHST- 2001/04/10 00:00 [revised]
PHST- 2001/04/19 00:00 [accepted]
PHST- 2001/07/21 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/07/21 10:00 [entrez]
AID - 10.1038/sj.onc.1204563 [doi]
PST - ppublish
SO  - Oncogene. 2001 Jul 12;20(31):4138-49. doi: 10.1038/sj.onc.1204563.