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The Cell Cycle and Androgen Signaling Interactions in Prostate Cancer

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Book cover Precision Molecular Pathology of Prostate Cancer

Part of the book series: Molecular Pathology Library ((MPLB))

Abstract

The essential role of androgen signaling in hormone-dependent and refractory prostate cancer is well established. Indeed, prostate cancer cells have long been known to co-opt androgen signaling to drive uncontrolled cellular replication and proliferation. To do this, androgen signaling must overcome stringent cell cycle checkpoints which normally ensure accurate DNA replication during the S (synthesis)-phase and chromosomal segregation during the M (mitosis)-phase. In non-malignant cells, the cell cycle is tightly regulated as the levels and composition of cyclin and cyclin-dependent kinase (CDK) complexes orchestrate the ordered transition from G1 (gap 1) phase to mitotic cell division. There is now compelling evidence that androgen signaling influences cell cycle progression by regulating the levels and functions of D-type cyclins and CDKs and also that components of the cell cycle apparatus influence androgen receptor (AR) function. Indeed, specific cell cycle regulators, including cyclin A1, Cyclin D1, cyclin E1, CDK7, and CDK9, are believed to be components of the dynamic AR-coregulator complex in prostate cancer cells. Therefore, establishing the mechanistic links between androgen signaling and cell cycle regulation and how these differ between nonmalignant and hormone-dependent versus hormone refractory prostate cancer cells is an area of active research. In this chapter, we will review current understanding of how androgen signaling influences the cell cycle in prostate cancer.

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Authors and Affiliations

  1. Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Science, University of Nottingham, Nottingham, UK

    Simone de Brot D.V.M., Dip. E.C.V.P. & Nigel P. Mongan B.Sc (Hons), Ph.D, F.R.CPath

  2. Department of Pharmacology, Weill Cornell Medicine, New York, NY, 10065, USA

    Nigel P. Mongan B.Sc (Hons), Ph.D, F.R.CPath

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  1. Simone de Brot D.V.M., Dip. E.C.V.P.
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  1. Pathology and Laboratory Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, New York, USA

    Brian D. Robinson

  2. Pathology and Laboratory Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, New York, USA

    Juan Miguel Mosquera

  3. Institute for Academic Medicine, Houston Methodist Hospital Pathology and Genomic Medicine, Weill Medical College of Cornell University, Houston, Texas, USA

    Jae Y. Ro

  4. Institute for Academic Medicine, Houston Methodist Hospital Pathology and Genomic Medicine, Weill Medical College of Cornell University, Houston, Texas, USA

    Mukul Divatia

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de Brot, S., Mongan, N.P. (2018). The Cell Cycle and Androgen Signaling Interactions in Prostate Cancer. In: Robinson, B., Mosquera, J., Ro, J., Divatia, M. (eds) Precision Molecular Pathology of Prostate Cancer. Molecular Pathology Library. Springer, Cham. https://doi.org/10.1007/978-3-319-64096-9_22

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