Immortal cell lines isolated from heart differentiate to an endothelial cell lineage in the presence of retinoic acid.
Previously, we isolated a single line of transgenic mice which develop an enlarged heart due to the expression of the immortalizing gene, polyomavirus large T antigen. Immortal cell lines were isolated from adult transgenic but not from nontransgenic hearts. All of the 24 cell lines expressed vimentin and fibronectin but not desmin or myosin heavy chain. We conclude that the cell lines are of non-muscle origin. Six cell lines were chosen for further study. All six cell lines demonstrate profound morphological and biochemical effects when incubated with 10(-4) M to 10(-7) M retinoic acid. The retinoic acid-treated cell lines showed arrested cellular proliferation and aligned to form rows and vesicle-like structures. Cycloheximide inhibited these retinoic acid-induced changes, indicating a need for continued protein synthesis. Retinoic acid-treated, but not untreated, cells lost expression of vimentin and fibronectin, gained the ability to incorporate acetylated low density lipoprotein, and expressed Factor VIII-related antigen. Retinoic acid did not induce expression of desmin or myosin heavy chain. Incubation of the cell lines with transforming growth factor beta 1, dimethyl sulfoxide, or phorbol esters had no biochemical or morphological effect. We conclude that these cell lines differentiate to an endothelial lineage in the presence of retinoic acid.
al Moustafa
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Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
Chalifour
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D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology; D010703:Phorbol Esters / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*
D010703:Phorbol Esters; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D004121:Dimethyl Sulfoxide