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Suppression of Neu-induced mammary tumor growth in cyclin D1 deficient mice is compensated for by cyclin E

Oncogene volume 21, pages 291–298 (2002)Cite this article

Abstract

Amplification and/or overexpression of the receptor tyrosine kinase HER2/Neu and the cell cycle regulatory gene cyclin D1 are frequently associated with human breast cancer. We studied the functional significance of cyclin D1 in Neu-induced mammary oncogenesis by developing mice overexpressing either wild-type or mutant Neu in a cyclin D1 deficient background. The absence of cyclin D1 suppresses mammary tumor formation induced by the wild-type or activated mutant form of Neu, which promote multi- and single-step progression of tumorigenesis, respectively. These data indicate that cyclin D1 is preferentially required for Neu-mediated signal transduction pathways in mammary oncogenesis. Significantly, 35% of mutant Neu/cyclin D1−/− mice regained mammary tumor potential due to compensation by cyclin E. Thus, shared targets of cyclins D1 and E are important in modulating Neu function in mammary tumorigenesis. Our results imply that the combinatorial inhibition of cyclins D1 and E might be useful in the treatment of malignancies induced by Neu.

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Acknowledgements

The authors would like to thank the following individuals for their critical review of the manuscript: DK Watson, DD Spyropoulos, L Obeid, TS Hsu and R Muise-Helmericks. We thank the following investigators for providing plasmids: P Sicinski, W Muller, C Sherr and J DeLoia.

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Authors and Affiliations

  1. Laboratory of Cancer Genomics, Hollings Cancer Center, Medical University of South Carolina, Charleston, 29425, South Carolina, SC, USA

    Damon B Bowe, Yair Adereth & Ioanna G Maroulakou

  2. Department of Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, 29425, South Carolina, SC, USA

    Ioanna G Maroulakou

  3. Department of Biological Sciences, Hampton University, Hampton, 23668, Virginia, VA, USA

    Nicholas J Kenney

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  1. Damon B Bowe
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Correspondence to Ioanna G Maroulakou.

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Bowe, D., Kenney, N., Adereth, Y. et al. Suppression of Neu-induced mammary tumor growth in cyclin D1 deficient mice is compensated for by cyclin E. Oncogene 21, 291–298 (2002). https://doi.org/10.1038/sj.onc.1205025

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