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Androgen Receptor Regulation of Prostate Cancer Progression and Metastasis

  • R. S. Schrecengost
  • M. A. Augello
  • Karen E. Knudsen
Chapter

Abstract

Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous malignancy and the second most lethal cancer in men amongst the United States. Localized tumors are effectively treated via radical prostatectomy and/or radiation therapy, however disseminated disease contributes greatly to patient morbidity. At present, therapeutic intervention for metastatic disease capitalizes on the addiction of these tumors to the androgen receptor (AR). The AR signaling axis regulates cell growth, proliferation, and migration of cancer cells, which makes understanding the contribution of AR toward these signaling pathways integral for PCa eradication. Several key signaling molecules are currently known to be controlled by AR and promote migration and invasion in castrate-resistant PCa (CRPC). This concept will be explored with regard to the interplay between AR and chemokine receptors, chromosomal fusions, oncogenes, and microRNAs. Additionally, current and preclinical AR-directed therapeutics used for treatment of metastatic PCa, which impinge on these pathways, and overall AR activity, will be discussed.

Keywords

Androgen Receptor Androgen Receptor Expression Abiraterone Acetate Androgen Receptor Signaling Ezrin Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

Abiraterone

Abiraterone acetate

ADT

Androgen deprivation therapy

AR

Androgen receptor

BC

Bicalutamide (Casodex)

CDKS

Cyclin-dependent kinases

CML

Chronic myelogenous leukemia

CRPC

Castration resistant prostate cancer

CTCs

Circulating tumor cells

DHT

5α-dihydrotestosterone

E-Box

Enhancer box

ETS

Erythroblast transformation specific transcription factor

FAK

Focal adhesion kinase

FISH

Florescence in-situ hybridization

Flutamide

Hydroxyflutamide

GnRH

Gonadotropin releasing hormone

HATs

Histone acetyltransferases

HSPs

Heat shock proteins

IHC

Immunohistochemistry

KLF5

Kruppel-like-factor 5

LBD

Ligand binding domain

MMPs

Matrix metalloproteinases

miRNA

MicroRNA

MYC

c-Myc

NCoR1

Nuclear Co-Repressor 1

PIN

Prostatic intraepithelial neoplasia

PcG

Polycomb-group

PCa

Prostate cancer

PSA

Prostate specific antigen

SDF-1

Stromal cell-derived factor 1

SFK

Macrophage inflammatory protein

SRC

Steroid receptor coactivator

TRAMP

Transgenic adenocarcinoma of the mouse prostate

TMPRSS2

Transmembrane protease serine 2

VCaP

Vertebral-Cancer of the Prostate

Notes

Acknowledgements

We would like to thank all the members of the K. Knudsen lab, especially M. Schiewer, for insightful feedback and critical reading of this chapter.

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • R. S. Schrecengost
    • 1
    • 2
  • M. A. Augello
    • 1
    • 2
  • Karen E. Knudsen
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of Cancer BiologyThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Kimmel Cancer Center, Thomas Jefferson UniversityPhiladelphiaUSA
  3. 3.Department of UrologyThomas Jefferson UniversityPhiladelphiaUSA
  4. 4.Department of Radiation OncologyThomas Jefferson UniversityPhiladelphiaUSA

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