TY - JOUR
T1 - Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells
AU - Ji, Ping
AU - Agrawal, Shuchi
AU - Diederichs, Sven
AU - Bäumer, Nicole
AU - Becker, Annette
AU - Cauvet, Thomas
AU - Kowski, Sascha
AU - Beger, Carmela
AU - Welte, Karl
AU - Berdel, Wolfgang E
AU - Serve, Hubert
AU - Müller-Tidow, Carsten
N1 - Keywords: Animals; Cell Proliferation; Cell Transformation, Neoplastic; Cyclin A; Cyclin A1; Female; G1 Phase; Gene Expression; Humans; Kinetics; Leukemia; Male; Mice; Mice, Knockout; NIH 3T3 Cells; Oligoribonucleotides; S Phase; U937 Cells
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1038/sj.onc.1208356
DO - 10.1038/sj.onc.1208356
M3 - Journal article
C2 - 15829981
SN - 0950-9232
VL - 24
SP - 2739
EP - 2744
JO - Oncogene
JF - Oncogene
IS - 16
ER -