title: Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells.
abstract: Cyclin A1 is an alternative A-type cyclin that is essential for spermatogenesis, but it is also expressed in hematopoietic progenitor cells and in acute myeloid leukemia. Its functions during cell cycle progression of somatic cells are incompletely understood. Here, we have analysed the cell cycle functions of cyclin A1 in transformed and nontransformed cells. Murine embryonic fibroblasts derived from cyclin A1-deficient mice were significantly impaired in their proliferative capacity. In accordance, cyclin A1-/- cells accumulated in G1 and G2/M phase while the percentage of S phase cells decreased. Also, lectin stimulated splenic lymphocytes from cyclin A1-/- mice proliferated slower than their wild-type counterparts. Forced cyclin A1 overexpression in NIH3T3 cells and in U937 leukemic cells either by transient transfection or by retroviral infection enhanced S phase entry. Consequently, siRNA mediated silencing of cyclin A1 in highly cyclin A1 expressing ML1 leukemic cells significantly slowed S phase entry, decreased proliferation and inhibited colony formation. Taken together, these analyses demonstrate that cyclin A1 contributes to G1 to S cell cycle progression in somatic cells. Cyclin A1 overexpression enhances S phase entry consistent with an oncogenic function. Finally, cyclin A1 might be a therapeutic target since its silencing inhibited leukemia cell growth.
authors.affiliation: Department of Medicine, Hematology/Oncology, University of Münster, Domagkstr. 3, 48149 Münster, Germany.
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.forename: Shuchi
authors.initials: S
authors.lastname: Agrawal
authors.forename: Sven
authors.initials: S
authors.lastname: Diederichs
authors.forename: Nicole
authors.initials: N
authors.lastname: Bäumer
authors.forename: Annette
authors.initials: A
authors.lastname: Becker
authors.forename: Thomas
authors.initials: T
authors.lastname: Cauvet
authors.forename: Sascha
authors.initials: S
authors.lastname: Kowski
authors.forename: Carmela
authors.initials: C
authors.lastname: Beger
authors.forename: Karl
authors.initials: K
authors.lastname: Welte
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D019925:Cyclin A / Q000235:genetics* / Q000378:metabolism; D056750:Cyclin A1; D005260:Female; D016193:G1 Phase; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009843:Oligoribonucleotides; D016196:S Phase; D020298:U937 Cells
chemical_list: C503745:CCNA1 protein, human; C503747:Ccna1 protein, mouse; D019925:Cyclin A; D056750:Cyclin A1; D009843:Oligoribonucleotides