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Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells

Oncogene volume 24, pages 2739–2744 (2005)Cite this article

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.

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Acknowledgements

This work is supported by grants from the Deutsche Forschungsgemeinschaft (Mu 1328/2-3, Se 600/3), the Deutsche Krebshilfe (10-1539-Mü3), the IMF and the IZKF at the University of Münster. C. Müller-Tidow is supported by the DFG-Heisenberg program (Mu1328/3-1).

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Authors and Affiliations

  1. Department of Medicine, Hematology/Oncology, University of Münster, Domagkstr. 3, 48149, Münster, Germany

    Ping Ji, Shuchi Agrawal, Sven Diederichs, Nicole Bäumer, Annette Becker, Thomas Cauvet, Wolfgang E Berdel, Hubert Serve & Carsten Müller-Tidow

  2. Department of Pediatric Hematology and Oncology, MHH Hannover, 30625, Hannover, Germany

    Sascha Kowski, Carmela Beger & Karl Welte

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  1. Ping Ji
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Correspondence to Carsten Müller-Tidow.

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Ji, P., Agrawal, S., Diederichs, S. et al. Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells. Oncogene 24, 2739–2744 (2005). https://doi.org/10.1038/sj.onc.1208356

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