title: Stromal androgen receptor in prostate development and cancer.
abstract: The androgen receptor (AR) in stromal cells contributes significantly to the development and growth of prostate during fetal stages as well as during prostate carcinogenesis and cancer progression. During prostate development, stromal AR induces and promotes epithelial cell growth, as observed from tissue recombinant and mouse knockout studies. During prostate carcinogenesis and progression, the stromal cells begin to lose AR expression as early as at the stage of high-grade prostatic intraepithelial neoplasia. The extent of loss of stromal AR is directly proportional to the degree of differentiation (Gleason grade) and progression of prostate cancer (PCa). Co-culture studies suggested that stromal AR inhibits the growth of malignant epithelial cells, possibly through expression of certain paracrine factors in the presence of androgens. This functional reversal of stromal AR, from growth promotion during fetal prostate development to mediating certain growth-inhibiting effects in cancer, explains to some extent the reason that loss of AR expression in stromal cells may be crucial for development of resistance to androgen ablation therapy for PCa. From a translational perspective, it generates the need to re-examine the current therapeutic options and opens a fundamental new direction for therapeutic interventions, especially in advanced PCa.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Mandeep
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Jha
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.affiliation: Department of Urology, New York University School of Medicine, New York, New York.
authors.forename: Ellen
authors.initials: E
authors.lastname: Shapiro
authors.affiliation: Departments of Urologic Surgery and Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: simon.hayward@vanderbilt.edu.
authors.forename: Simon W
authors.initials: SW
authors.lastname: Hayward
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York; Department of Urology, New York University School of Medicine, New York, New York; New York Harbor Healthcare System, New York University School of Medicine, New York, New York. Electronic address: peng.lee@nyumc.org.
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
mesh_terms: D000728:Androgens / Q000378:metabolism*; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C410798:AR protein, human; D000728:Androgens; D011944:Receptors, Androgen
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