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Differential expression of estrogen receptor beta isoforms in prostate cancer through interplay between transcriptional and translational regulation.

ABSTRACT: Estrogen receptor ? (ER?) and its isoforms have different putative functions and expression patterns in prostate cancer. Current studies on 5'-most exons, 0K and 0N, show that their respective promoters are actively involved in transcription. These data, however, do not explain why ER? isoforms are differentially expressed in normal and cancerous tissues, since 0K and 0N transcripts are detectable in clinical specimens. Various combinations of 5' untranslated exons, termed exon 0Xs, associate with promoter 0K only and exon 0Xs accommodate upstream open reading frames (uORFs) reducing protein expression. Moreover, ER?1, 2, and 5 are transcriptionally linked to promoter 0K; exon 0Xs are spliced only into ER?2 and ER?5 transcripts, suggesting that their expressions are regulated post-transcriptionally by exon 0Xs. This study reveals that expression of ER?1 is regulated primarily at the transcriptional level, whereas that of ER?2 and ER?5 is controlled by the interplay between transcriptional and post-transcriptional regulation.

SUBMITTER: Lee MT

PROVIDER: S-EPMC4319372 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Differential expression of estrogen receptor beta isoforms in prostate cancer through interplay between transcriptional and translational regulation.

Lee Ming-Tsung MT Ouyang Bin B Ho Shuk-Mei SM Leung Yuet-Kin YK

Molecular and cellular endocrinology 20130624 1-2

Estrogen receptor β (ERβ) and its isoforms have different putative functions and expression patterns in prostate cancer. Current studies on 5'-most exons, 0K and 0N, show that their respective promoters are actively involved in transcription. These data, however, do not explain why ERβ isoforms are differentially expressed in normal and cancerous tissues, since 0K and 0N transcripts are detectable in clinical specimens. Various combinations of 5' untranslated exons, termed exon 0Xs, associate wi ...[more]

PMID: 23806560

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Project description:Recent researches have shown that estrogen receptor-β (ERβ) activator may be a potent anticancer agent for prostate cancer (PCa), and our previous study also indicated that dioscin can upregulate the expression of ERβ in MC3T3-E1 cell. In the present work, the activity and mechanism of dioscin, a natural product, against PCa were investigated. The results showed that dioscin markedly inhibited cell viability, colony formation, motility and induced apoptosis in PC3 cells. Moreover, dioscin disrupted the formation of PC3 cell-derived mammospheres and reduced aldehyde dehydrogenase (ALDH) level and the CD133+/CD44+ cells, indicating that dioscin had a potent inhibitory activity on prostate cancer stem cells (PCSCs). In vivo results also showed that dioscin significantly suppressed the tumor growth of PC3 cell xenografts in nude mice. Furthermore, mechanism investigation showed that dioscin markedly upregulated ERβ expression level, subsequently increased prolyl hydroxylase 2 level, decreased the levels of hypoxia-inducible factor-1α, vascular endothelial growth factor A and BMI-1, and thus induced cell apoptosis by regulating the expression levels of caspase-3 and Bcl-2 family proteins. In addition, transfection experiment of ERβ-siRNA further indicated that diosicn showed excellent activity against PCa in vitro and in vivo by increasing ERβ expression level. The co-immunoprecipitation (Co-IP) results further suggested that dioscin promoted the interaction of c-ABL and ERβ, but did not change c-ABL expression. Moreover, the molecular docking assay showed that dioscin processed powerful affinity toward to ERβ mainly through the strong hydrogen bonding and hydrophobic effects, and the actions of dioscin on ERβ activation and tumor cells inhibition were significantly weakened in the mutational (Phe-336, Phe-468) PC3 cells. Collectively, these findings proved that dioscin exerted efficient anti-PCa activity via activation of ERβ, which should be developed as an efficient candidate in clinical for treating this cancer in the future.

Dataset Information

Differential expression of estrogen receptor beta isoforms in prostate cancer through interplay between transcriptional and translational regulation.

Publications

Differential expression of estrogen receptor beta isoforms in prostate cancer through interplay between transcriptional and translational regulation.

Similar Datasets

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