Retinoid-enhanced gap junctional communication is achieved by increased levels of connexin 43 mRNA and protein.
Natural and synthetic retinoids are potent inhibitors of experimental carcinogenesis in animals and cause reversion of premalignant lesions in humans. In the model C3H 10T1/2 cell system, retinoids enhance postconfluent growth control, reversibly inhibit carcinogen-induced transformation, and enhance gap junctional intercellular communication. These effects are highly correlated. 10T1/2 cells were found to express low levels of connexin 43, a gap junctional protein first found in the heart. After treatment of confluent 10T1/2 cells with the synthetic retinoid tetrahydrotetramethylnapthalenylpropenylbenzoic acid (TTNPB), levels of connexin 43 mRNA and protein increased within 6 h of treatment, while elevation of junctional communication was detected within 12-18 h. The maximally effective concentration of TTNPB (10(-8) M) caused an approximate 10-fold elevation of connexin 43 gene transcripts after 72 h. Indirect immunofluorescence microscopy using a polyclonal antibody to the synthetic C-terminal region of connexin 43 demonstrated that TTNPB induced many fluorescent plaques in regions of cell-cell contact. These results provide a molecular basis for the retinoid-enhanced junctional communication in 10T1/2 cells. It is proposed that one action of retinoids is to modulate the intercellular transfer of signal molecules. These could mediate many of the physiological actions of retinoids on growth control and carcinogenesis.
Rogers
M
M
Basic Science Program, University of Hawaii, Honolulu 96813.
Berestecky
J M
JM
Hossain
M Z
MZ
Guo
H M
HM
Kadle
R
R
Nicholson
B J
BJ
Bertram
J S
JS
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D017630:Connexins; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D007365:Intercellular Junctions / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D012176:Retinoids / Q000494:pharmacology*; D013997:Time Factors
D001565:Benzoates; D017630:Connexins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D012176:Retinoids; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid