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Retinoid‐enhanced gap junctional communication is achieved by increased levels of connexin 43 mRNA and protein
Author(s) -
Rogers Michael,
Berestecky John M.,
Hossain Mohammad Z.,
Guo Huiming,
Kadle Ranjana,
Nicholson Bruce J.,
Bertram John S.
Publication year - 1990
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940030605
Subject(s) - connexin , biology , gap junction , retinoid , microbiology and biotechnology , intracellular , retinoic acid , carcinogenesis , cell culture , biochemistry , gene , genetics
Abstract 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.