title: Increased expression of cyclin A1 protein is associated with all-trans retinoic acid-induced apoptosis.
abstract: Deregulated cell growth and inhibition of apoptosis are hallmarks of cancer. All-trans retinoic acid induces clinical remission in patients with acute promyelocytic leukemia by inhibiting cell growth and inducing differentiation and apoptosis of the leukemic blasts. An important role of the cell cycle regulatory protein, cyclin A1, in the development of acute myeloid leukemia has previously been demonstrated in a transgenic mouse model. We have recently shown that there was a direct interaction between cyclin A1 and a major all-trans retinoic acid receptor, RAR alpha, following all-trans retinoic acid treatment of leukemic cells. In the present study, we investigated whether cyclin A1 might be involved in all-trans retinoic acid-induced apoptosis in U-937 leukemic cells. We found that all-trans retinoic acid-induced apoptosis was associated with concomitant increase in cyclin A1 expression. However, there was no induction of cyclin A1 mRNA expression following the all-trans retinoic acid-induced apoptosis. Treatment of cells with a caspase inhibitor was not able to prevent all-trans retinoic acid-induced up-regulation of cyclin A1 expression. Interestingly, induced cyclin A1 expression in U-937 cells led to a significant increase in the proportion of apoptotic cells. Further, U-937 cells overexpressing cyclin A1 appeared to be more sensitive to all-trans retinoic acid-induced apoptosis indicating the ability of cyclin A1 to mediate all-trans retinoic acid-induced apoptosis. Induced cyclin E expression was not able to initiate cell death in U-937 cells. Our results indicate that cyclin A1 might have a role in apoptosis by mediating all-trans retinoic acid-induced apoptosis.
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Lund University, University Hospital, 205 02 Malmö, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ekberg
authors.forename: Cecilia
authors.initials: C
authors.lastname: Brunhoff
authors.forename: Marcus
authors.initials: M
authors.lastname: Järås
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Fan
authors.forename: Göran
authors.initials: G
authors.lastname: Landberg
authors.forename: Jenny Liao
authors.initials: JL
authors.lastname: Persson
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism*; D056750:Cyclin A1; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: C503745:CCNA1 protein, human; D019925:Cyclin A; D056750:Cyclin A1; D012333:RNA, Messenger; D014212:Tretinoin