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Epithelial-to-mesenchymal transition and estrogen receptor α mediated epithelial dedifferentiation mark the development of benign prostatic hyperplasia.
Prostate 2014; 74(9):970-82P

Abstract

BACKGROUND

Epithelial-to-mesenchymal transition (EMT) has been reported involved in the pathogenesis of fibrotic disorders and associated with stemness characteristics. Recent studies demonstrated that human benign prostatic hyperplasia (BPH) development involves accumulation of mesenchymal-like cells derived from the prostatic epithelium. However, the inductive factors of EMT in the adult prostate and the cause-and-effect relationship between EMT and stemness characteristics are not yet resolved.

METHODS

EMT expression patterns were immunohistochemically identified in the human epithelia of normal/BPH prostate tissue and in a rat BPH model induced by estrogen/androgen (E2/T, ratio 1:100) alone or in the presence of the ER antagonist raloxifene. Gene expression profiles were analyzed in micro-dissected prostatic epithelia of rat stimulated by E2/T for 3 days.

RESULTS

Two main morphological features both accompanied with EMT were observed in the epithelia of human BPH. Luminal cells undergoing EMT dedifferentiated from a cytokeratin (CK) CK18(+) /CK8(+) /CK19(+) to a CK18(-) /CK8(+) /CK19(-) phenotype and CK14 expression increased in basal epithelial cells. ERα expression was closely related to these dedifferentiated cells and the expression of EMT markers. A similar pattern of EMT events was observed in the E2/T induced rat model of BPH in comparison to the prostates of untreated rats, which could be prevented by raloxifene.

CONCLUSIONS

Epithelial and mesenchymal phenotype switching is an important mechanism in the etiology of BPH. ERα mediated enhanced estrogenic effect is a crucial inductive factor of epithelial dedifferentiation giving rise to activation of an EMT program in prostate epithelium.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24752964

Citation

Shao, Rui, et al. "Epithelial-to-mesenchymal Transition and Estrogen Receptor Α Mediated Epithelial Dedifferentiation Mark the Development of Benign Prostatic Hyperplasia." The Prostate, vol. 74, no. 9, 2014, pp. 970-82.
Shao R, Shi J, Liu H, et al. Epithelial-to-mesenchymal transition and estrogen receptor α mediated epithelial dedifferentiation mark the development of benign prostatic hyperplasia. Prostate. 2014;74(9):970-82.
Shao, R., Shi, J., Liu, H., Shi, X., Du, X., Klocker, H., ... Zhang, J. (2014). Epithelial-to-mesenchymal transition and estrogen receptor α mediated epithelial dedifferentiation mark the development of benign prostatic hyperplasia. The Prostate, 74(9), pp. 970-82. doi:10.1002/pros.22814.
Shao R, et al. Epithelial-to-mesenchymal Transition and Estrogen Receptor Α Mediated Epithelial Dedifferentiation Mark the Development of Benign Prostatic Hyperplasia. Prostate. 2014;74(9):970-82. PubMed PMID: 24752964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epithelial-to-mesenchymal transition and estrogen receptor α mediated epithelial dedifferentiation mark the development of benign prostatic hyperplasia. AU - Shao,Rui, AU - Shi,Jiandang, AU - Liu,Haitao, AU - Shi,Xiaoyu, AU - Du,Xiaoling, AU - Klocker,Helmut, AU - Lee,Chung, AU - Zhu,Yan, AU - Zhang,Ju, Y1 - 2014/04/22/ PY - 2014/01/03/received PY - 2014/03/29/accepted PY - 2014/4/23/entrez PY - 2014/4/23/pubmed PY - 2014/7/2/medline KW - benign prostatic hyperplasia KW - embryonic myosin KW - epithelial-mesenchymal transition KW - estrogen receptor α SP - 970 EP - 82 JF - The Prostate JO - Prostate VL - 74 IS - 9 N2 - BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has been reported involved in the pathogenesis of fibrotic disorders and associated with stemness characteristics. Recent studies demonstrated that human benign prostatic hyperplasia (BPH) development involves accumulation of mesenchymal-like cells derived from the prostatic epithelium. However, the inductive factors of EMT in the adult prostate and the cause-and-effect relationship between EMT and stemness characteristics are not yet resolved. METHODS: EMT expression patterns were immunohistochemically identified in the human epithelia of normal/BPH prostate tissue and in a rat BPH model induced by estrogen/androgen (E2/T, ratio 1:100) alone or in the presence of the ER antagonist raloxifene. Gene expression profiles were analyzed in micro-dissected prostatic epithelia of rat stimulated by E2/T for 3 days. RESULTS: Two main morphological features both accompanied with EMT were observed in the epithelia of human BPH. Luminal cells undergoing EMT dedifferentiated from a cytokeratin (CK) CK18(+) /CK8(+) /CK19(+) to a CK18(-) /CK8(+) /CK19(-) phenotype and CK14 expression increased in basal epithelial cells. ERα expression was closely related to these dedifferentiated cells and the expression of EMT markers. A similar pattern of EMT events was observed in the E2/T induced rat model of BPH in comparison to the prostates of untreated rats, which could be prevented by raloxifene. CONCLUSIONS: Epithelial and mesenchymal phenotype switching is an important mechanism in the etiology of BPH. ERα mediated enhanced estrogenic effect is a crucial inductive factor of epithelial dedifferentiation giving rise to activation of an EMT program in prostate epithelium. SN - 1097-0045 UR - https://www.unboundmedicine.com/medline/citation/24752964/Epithelial_to_mesenchymal_transition_and_estrogen_receptor_α_mediated_epithelial_dedifferentiation_mark_the_development_of_benign_prostatic_hyperplasia_ L2 - https://doi.org/10.1002/pros.22814 DB - PRIME DP - Unbound Medicine ER -