Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma
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Authors
Leav, IrwinLau, Kin-Mang
Adams, Jason Y.
McNeal, John E.
Taplin, Mary-Ellen
Wang, Jianfu
Singh, Hema
Ho, Shuk-Mei
UMass Chan Affiliations
Department of Surgery, Division of UrologyDepartment of Pathology
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2001-07-05Keywords
Aged; Blotting, Western; Carcinoma; Enzyme-Linked Immunosorbent Assay; Estrogen Receptor alpha; Estrogen Receptor beta; Humans; Immunochemistry; Immunohistochemistry; Male; Middle Aged; Prostate; Prostatic Diseases; Prostatic Neoplasms; RNA, Messenger; Receptors, Androgen; Receptors, Estrogen; Reference Values; Reverse Transcriptase Polymerase Chain ReactionLife Sciences
Medicine and Health Sciences
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Show full item recordAbstract
An antibody, GC-17, thoroughly characterized for its specificity for estrogen receptor-beta (ER-beta), was used to immunolocalize the receptor in histologically normal prostate, prostatic intraepithelial neoplasia, primary carcinomas, and in metastases to lymph nodes and bone. Comparisons were made between ER-beta, estrogen receptor-alpha (ER-alpha), and androgen receptor (AR) immunostaining in these tissues. Concurrently, transcript expression of the three steroid hormone receptors was studied by reverse transcriptase-polymerase chain reaction analysis on laser capture-microdissected samples of normal prostatic acini, dysplasias, and carcinomas. In Western blot analyses, GC-17 selectively identified a 63-kd protein expressed in normal and malignant prostatic epithelial cells as well as in normal testicular and prostatic tissues. This protein likely represents a posttranslationally modified form of the long-form ER-beta, which has a predicted size of 59 kd based on polypeptide length. In normal prostate, ER-beta immunostaining was predominately localized in the nuclei of basal cells and to a lesser extent stromal cells. ER-alpha staining was only present in stromal cell nuclei. AR immunostaining was variable in basal cells but strongly expressed in nuclei of secretory and stromal cells. Overall, prostatic carcinogenesis was characterized by a loss of ER-beta expression at the protein and transcript levels in high-grade dysplasias, its reappearance in grade 3 cancers, and its diminution/absence in grade 4/5 neoplasms. In contrast, AR was strongly expressed in all grades of dysplasia and carcinoma. Because ER-beta is thought to function as an inhibitor of prostatic growth, androgen action, presumably mediated by functional AR and unopposed by the beta receptor, may have provided a strong stimulus for aberrant cell growth. With the exception of a small subset of dysplasias in the central zone and a few carcinomas, ER-alpha-stained cells were not found in these lesions. The majority of bone and lymph node metastases contained cells that were immunostained for ER-beta. Expression of ER-beta in metastases may have been influenced by the local microenvironment in these tissues. In contrast, ER-alpha-stained cells were absent in bone metastases and rare in lymph nodes metastases. Irrespective of the site, AR-positive cells were found in all metastases. Based on our recent finding of anti-estrogen/ER-beta-mediated growth inhibition of prostate cancer cells in vitro, the presence of ER-beta in metastatic cells may have important implications for the treatment of late-stage disease.Source
Am J Pathol. 2001 Jul;159(1):79-92.
DOI
10.1016/S0002-9440(10)61676-8Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33999PubMed ID
11438457Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/S0002-9440(10)61676-8
Scopus Count
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