Comparison of glucocorticoid-mediated changes in the expression and function of rat hepatocyte gap junctional proteins.
Gap junctional intercellular communication (GJIC) is often modulated by chemical carcinogens and during carcinogenesis, in part, through changes in gap junction mRNA levels. However, the mechanisms by which gap junction mRNA levels are altered in either normal or cancer cells are largely unknown. Since glucocorticoids are potent modulators of gene expression and stability, we have investigated the effects of these hormones on GJIC and gap junction mRNA expression in rat hepatocytes cultured in three different media. Addition of dexamethasone to cultures of rat hepatocytes resulted in a maintenance of GJIC and both major liver gap junctional mRNAs, connexin (Cx)26 and Cx32, at levels above those in hepatocytes cultured in glucocorticoid-free media. In addition, hepatocytes cultured without dexamethasone for 24 h could be induced to communicate and increase Cx mRNA levels by the addition of dexamethasone to their medium. These media-independent changes in GJIC and gap junction mRNA levels by dexamethasone warrant further investigations into their mechanisms of action and the potential therapeutic value of glucocorticoids in the treatment of cancer.
Kwiatkowski
A P
AP
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202.
Baker
T K
TK
Klaunig
J E
JE
D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
D017630:Connexins; D012333:RNA, Messenger; D003907:Dexamethasone