Estrogen receptor β2 and β5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion

Yuet Kin Leung, Hung Ming Lam, Shulin Wu, Dan Song, Linda Levin, Liang Cheng, Chin Lee Wu, Shuk Mei Ho

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Estrogens play a pivotal role in the development and progression of prostate cancer (PCa). Their actions are mediated by estrogen receptors (ERs), particularly ERβ in the prostate epithelium. With the discovery of ERβ isoforms, data from previous studies that focused principally on the wild-type ERβ (ERβ1) may not be adequate in explaining the still controversial role of ERβ(s) in prostate carcinogenesis. In this study, using newly generated isoform-specific antibodies, immunohistochemistry (IHC) was performed on a tumor microarray comprised of 144 specimens. IHC results were correlated with pathological and clinical follow-up data to delineate the distinct roles of ERβ1, ERβ2, and ERβ5 in PCa. ERβ2 was commonly found in the cytoplasm and was the most abundant isoform followed by ERβ1 localized predominantly in the nucleus, and ERβ5 was primarily located in the cytoplasm. Logistic regression analyses demonstrated that nuclear ERβ2 (nERβ2) is an independent prognostic marker for prostate specific antigen (PSA) failure and postoperativemetastasis (POM). In a Kaplan-Meier analysis, the combined expression of both nERβ2 and cytoplasmic ERβ5 identified a group of patients with the shortest POM-free survival. Cox proportional hazard models revealed that nERβ2 predicted shorter time to POM. In concordance with IHC data, stable, ectopic expression of ERβ2 or ERβ5 enhanced PCa cell invasiveness but only PCa cells expressing ERβ5 exhibited augmented cell migration. This is the first study to uncover a metastasis-promoting role of ERβ2 and ERβ5 in PCa, and show that the two isoforms, singularly and conjointly, have prognostic values for PCa progression. These findings may aid future clinical management of PCa.

Original languageEnglish
Pages (from-to)675-689
Number of pages15
JournalEndocrine-Related Cancer
Volume17
Issue number3
DOIs
StatePublished - Sep 2010

Fingerprint

Estrogen Receptor beta
Cell Movement
Prostatic Neoplasms
Estrogen Receptors
Protein Isoforms
Neoplasms
Immunohistochemistry
Prostate
Cytoplasm
Kaplan-Meier Estimate
Prostate-Specific Antigen
Proportional Hazards Models
Estrogens
Carcinogenesis
Epithelium
Logistic Models
Regression Analysis
Neoplasm Metastasis
Survival
Antibodies

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Estrogen receptor β2 and β5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion. / Leung, Yuet Kin; Lam, Hung Ming; Wu, Shulin; Song, Dan; Levin, Linda; Cheng, Liang; Wu, Chin Lee; Ho, Shuk Mei.

In: Endocrine-Related Cancer, Vol. 17, No. 3, 09.2010, p. 675-689.

Research output: Contribution to journalArticle

Leung, Yuet Kin ; Lam, Hung Ming ; Wu, Shulin ; Song, Dan ; Levin, Linda ; Cheng, Liang ; Wu, Chin Lee ; Ho, Shuk Mei. / Estrogen receptor β2 and β5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion. In: Endocrine-Related Cancer. 2010 ; Vol. 17, No. 3. pp. 675-689.
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