Differential regulation of oestrogen receptor β isoforms by 5′ untranslated regions in cancer

Smith, Laura; Brannan, R.; Hanby, Andrew M.; Shaaban, Abeer M.; Verghese, Eldo T.; Peter, Mark; Pollock, Steven; Satheesha, Sampoorna; Szynkiewicz, Marcin; Speirs, Valerie; Hughes, Tom

doi:10.1111/j.1582-4934.2009.00867.x

Cited by 30 publications

(62 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The absence of amplification was not due to poor primer design because the primer pair was able to amplify promoter 0N-initiated ERβ5 transcript in the breast cancer cell line MDA-MB-231 (Fig. 4C, lower panel, right), a finding consistent with that of another group (Smith et al, 2010a). Moreover, BPH-1, which has high expression of ERβ5 (Fig.…”

Section: Resultssupporting

confidence: 81%

“…Studies of the prostate have revealed that ERβ transcripts are derived primarily from two promoters, 0K and 0N (Zhang et al, 2007; Zhu et al, 2004), although additional promoters (E1 and M) have been identified in other tissues (Shoda et al, 2002; Smith et al, 2010a). The promoters were named by the different 5′-most untranslated exons (0K and 0N) upstream of exon 1 (Hirata et al, 2001; Zhao et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Differential expression of ERβ1 and its isoforms in the prostate may also be related to post-transcriptional regulatory mechanisms, such as inhibition of protein translation by upstream open reading frames (uORFs) (Calvo et al, 2009), as reported in a study of breast cancer cells (Smith et al, 2010a). An mRNA has multiple uORFs, defined as sequences flanked by a pair of in-frame start and stop codons and within 5′ untranslated region (5′ UTR).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Lee¹,

Ouyang²,

Ho³

et al. 2013

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

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 with promoter 0K only and exon 0Xs accommodate upstream open reading frames (uORFs) reducing protein expression. Moreover, ERβ1, 2, and 5 are transcriptionally linked to promoter 0K; exon 0Xs are spliced only into ERβ2 and ERβ5 transcripts, suggesting that their expressions are regulated post-transcriptionally by exon 0Xs. This study reveals that expression of ERβ1 is regulated primarily at the transcriptional level, whereas that of ERβ2 and ERβ5 is controlled by the interplay between transcriptional and post-transcriptional regulation.

show abstract

Section: Resultssupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Lee¹,

Ouyang²,

Ho³

et al. 2013

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

show abstract

“…This could indicate complex ER␤ regulation, which our group has recently reported. 33 Alternatively, this may depend on the proportion of ER␤ isoforms within a given cell as only ER␤1 can bind ligand. 4 Heterodimerization with other non-ligand binding isoforms or with ER␣, 34 -36 which is abundantly expressed in MCF-7, may also influence this.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of Estrogen Receptor β at Serine 105 Is Associated with Good Prognosis in Breast Cancer

Hamilton-Burke

Coleman

Cummings

et al. 2010

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Estrogen receptor (ER) action is modulated by posttranslational modifications. Although ER␣ phosphorylation correlates with patient outcome, ER␤ is similarly phosphorylated but its significance in breast cancer has not been addressed. We investigated whether ER␤ that is phosphorylated at serine 105 (S105-ER␤) is expressed in breast cancer and assessed potential clinical implications of this phosphorylation. Following antibody validation, S105-ER␤ expression was studied in tissue microarrays comprising 108 tamoxifen-resistant and 351 tamoxifen-sensitive cases and analyzed against clinical data. S105-ER␤ regulation in vitro was assessed by Western blot, flow cytometry, and immunofluorescence. Nuclear S105-ER␤ was observed in breast carcinoma and was associated with better survival (Allred score >3), even in tamoxifen-resistant cases, and additionally correlated with ER␤1 and ER␤2 expression. Distinct S105-ER␤ nuclear speckles were seen in some higher grade tumors. S105-ER␤ levels increased in MCF-7 cells in response to 17␤-estradiol, the ER␤-specific agonist diarylpropionitrile , and the partial ER␤-agonist genistein. S105-ER␤ nuclear speckles were also seen in MCF-7 cells and markedly increased in size and number at 24 hours following 17␤-estradiol and, in particular diarylpropionitrile, treatment. These speckles were coexpressed with ER␤1 and ER␤2. Presence of S105-ER␤ in breast cancer and association with improved survival, even in endocrine resistant breast tumors suggest S105-ER␤ might be a useful additional prognostic marker in this disease.

show abstract

“…Such alternative TLs have been shown to confer differences in TE and regulation in a handful of cases, though the generality of this phenomenon is unknown (Rosenstiel et al 2007;Smith et al 2009). Many of these 230 genes showed distinct polysome sedimentation patterns.…”

Section: Intragenic Tl Heterogeneity Can Have Consequences For Translmentioning

confidence: 99%

Roles for transcript leaders in translation and mRNA decay revealed by transcript leader sequencing

2013

View full text Add to dashboard Cite

Transcript leaders (TLs) can have profound effects on mRNA translation and stability. To map TL boundaries genomewide, we developed TL-sequencing (TL-seq), a technique combining enzymatic capture of m 7 G-capped mRNA 59 ends with high-throughput sequencing. TL-seq identified mRNA start sites for the majority of yeast genes and revealed many examples of intragenic TL heterogeneity. Surprisingly, TL-seq identified transcription initiation sites within 6% of proteincoding regions, and these sites were concentrated near the 59 ends of ORFs. Furthermore, ribosome density analysis showed these truncated mRNAs are translated. Translation-associated TL-seq (TATL-seq), which combines TL-seq with polysome fractionation, enabled annotation of TLs, and simultaneously assayed their function in translation. Using TATLseq to address relationships between TL features and translation of the downstream ORF, we observed that upstream AUGs (uAUGs), and no other upstream codons, were associated with poor translation and nonsense-mediated mRNA decay (NMD). We also identified hundreds of genes with very short TLs, and demonstrated that short TLs were associated with poor translation initiation at the annotated start codon and increased initiation at downstream AUGs. This frequently resulted in out-of-frame translation and subsequent termination at premature termination codons, culminating in NMD of the transcript. Unlike previous approaches, our technique enabled observation of alternative TL variants for hundreds of genes and revealed significant differences in translation in genes with distinct TL isoforms. TL-seq and TATLseq are useful tools for annotation and functional characterization of TLs, and can be applied to any eukaryotic system to investigate TL-mediated regulation of gene expression.

show abstract

Differential regulation of oestrogen receptor β isoforms by 5′ untranslated regions in cancer

Cited by 30 publications

References 64 publications

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

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

Phosphorylation of Estrogen Receptor β at Serine 105 Is Associated with Good Prognosis in Breast Cancer

Roles for transcript leaders in translation and mRNA decay revealed by transcript leader sequencing

Contact Info

Product

Resources

About