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Delayed mammary gland involution in MMTV-AKT1 transgenic mice

Oncogene volume 21, pages 198–206 (2002)Cite this article

Abstract

AKT1/protein kinase Bα is a protein-serine/threonine kinase that regulates multiple targets involved in cell survival and cell cycle progression in a variety of cell types including breast cancer cells. To explore the role of Akt1 in mammary gland function and tumorigenesis, transgenic mice were generated that express human AKT1 under the control of the MMTV promoter. Virgin transgenic mice did not exhibit a dominant phenotype, but upon cessation of lactation, a notable delay in involution occurred compared to age-matched non-transgenic mice. The delay in involution coincided with increased hyperplasia as evidenced by an increased number of binucleated epithelial cells and a marked elevation in cyclin D1 expression in mammary epithelium. The delayed involution phenotype corresponded to increased phosphorylation of Thr308 in AKT1 and Ser136 in BAD, but not phosphorylation of Ser21 in GSK-3α. There was no evidence of mammary dysplasia or neoplasia during the lifespan of multiparous transgenic mice. These data suggest that AKT1 is involved in cell survival in the lactating and involuting mammary gland, but that overexpression of AKT1 alone is insufficient to induce transformation.

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Acknowledgements

S Ackler was supported by Predoctoral Fellowship DAMD17-00-1-0258 from the US Army Breast Cancer Research Program. This work was supported by NIH grant R01 CA881565 and by DAMD17-99-9195 from the US Army Breast Cancer Research Program (RI Glazer). The Lombardi Cancer Center Transgenic Shared Resource and Tissue Culture Shared Resources are supported by NIH grants P50-CA58185 and P30-CA51008. The authors would also like to acknowledge Dr Sandy McLeskey for assistance with the immunohistochemical staining techniques.

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Authors and Affiliations

  1. Department of Pharmacology, Georgetown University School of Medicine and Lombardi Cancer Center, Washington, 20007, DC, USA

    Scott Ackler & Robert I Glazer

  2. Department of Oncology, Georgetown University School of Medicine, and Lombardi Cancer Center, Washington, 20007, DC, USA

    Shakeel Ahmad, Christopher Tobias, Michael D Johnson & Robert I Glazer

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  1. Scott Ackler
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  2. Shakeel Ahmad
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Correspondence to Robert I Glazer.

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Ackler, S., Ahmad, S., Tobias, C. et al. Delayed mammary gland involution in MMTV-AKT1 transgenic mice. Oncogene 21, 198–206 (2002). https://doi.org/10.1038/sj.onc.1205052

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