RGD Reference Report - Opposing roles of ERalpha and ERbeta in the genesis and progression of adenocarcinoma in the rat ventral prostate. - Rat Genome Database

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Opposing roles of ERalpha and ERbeta in the genesis and progression of adenocarcinoma in the rat ventral prostate.

Authors: Attia, DM  Ederveen, AG 
Citation: Attia DM and Ederveen AG, Prostate. 2012 Jun 15;72(9):1013-22. doi: 10.1002/pros.21507. Epub 2011 Oct 24.
RGD ID: 8553211
Pubmed: PMID:22025007   (View Abstract at PubMed)
DOI: DOI:10.1002/pros.21507   (Journal Full-text)

BACKGROUND: Prostate cancer is a common malignancy in men and although hormone ablation therapy is effective, men develop hormone resistance. There is need for therapies applicable earlier, such as treatment of prostatic intraepithelial neoplasia (PIN). Estrogens besides androgens play a role in prostate cancer pathogenesis via two receptors ERalpha and ERbeta and both receptors are thought to play different, opposing, roles with ERalpha having proliferative properties and ERbeta having anti-proliferative properties. To differentiate between the roles both receptors play in prostate cancer an ERalpha and an ERbeta agonist, ERA-45 and ERB-26, have been tested in a rodent model for prostate carcinogenesis. METHODS: The influence of ERalpha on prostate cancer progression was studied in intact male rats treated with testosterone in combination with the ERalpha agonist, ERA-45 for either a long-term (20-week) period or a shorter term (6-week) period. The ERbeta agonist was tested in the shorter term model in intact male rats treated with testosterone in combination with the ERalpha agonist, ERA-45, followed by administration of the ERbeta agonist, ERB-26, during the last 2 weeks. RESULTS: Treatment of rats with testosterone in combination with ERA-45 induced mild PIN lesions at 6 weeks and severe precancerous PIN lesions at 20 weeks. The ERbeta agonist prevented the onset of PIN lesions at 6 weeks. Moreover, prostate epithelial cell apoptosis was increased and proliferation was decreased. CONCLUSION: These findings confirm the opposing roles ERalpha and ERbeta play in prostate carcinogenesis and suggest a therapeutic opportunity of ERbeta for treating precancerous PIN lesions.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of apoptotic process  IDA 8553211 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Esr1  (estrogen receptor 1)
Esr2  (estrogen receptor 2)

Genes (Mus musculus)
Esr1  (estrogen receptor 1 (alpha))
Esr2  (estrogen receptor 2 (beta))

Genes (Homo sapiens)
ESR1  (estrogen receptor 1)
ESR2  (estrogen receptor 2)


Additional Information