Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression)

Seth, Pankaj; Krop, Ian E.; Polyák, Kornélia

doi:10.1038/sj.onc.1205113

Cited by 102 publications

(86 citation statements)

References 34 publications

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“…We therefore studied BT-474 cells in which PHD1 protein expression was relatively high under basal conditions (see Fig. 2B), and in which induction of PHD1 mRNA by estrogen stimulation had been reported (37). Following estrogen stimulation PHD1, but not PHD2 or PHD3, protein level was further induced ϳ2.5-fold (Fig.…”

Section: Phd Isoforms 1-3 Contribute To the Regulation Of Hif-1␣ Undementioning

confidence: 85%

“…In particular relative PHD1 protein levels were substantially lower than predicted by relative PHD1 mRNA levels and were barely detectable in many cell lines. As other work had highlighted the expression of PHD1 mRNA in breast carcinoma BT-474 cells (37), and in the testis (29), we also examined BT-474 cells, and two other cell lines (833K and SuSa) of testicular origin (Fig. 2, B and C).…”

Section: Phd Isoforms Manifest Distinct Patterns Of Cellular Expression-mentioning

confidence: 99%

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Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor

Appelhoff

Tian

Raval

et al. 2004

Journal of Biological Chemistry

966

914

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Hypoxia-inducible factor (HIF) is a transcriptional regulator that plays a key role in many aspects of oxygen homeostasis. The heterodimeric HIF complex is regulated by proteolysis of its ␣-subunits, following oxygendependent hydroxylation of specific prolyl residues. Although three HIF prolyl hydroxylases, PHD1, PHD2, and PHD3, have been identified that have the potential to catalyze this reaction, the contribution of each isoform to the physiological regulation of HIF remains uncertain. Here we show using suppression by small interference RNA that each of the three PHD isoforms contributes in a non-redundant manner to the regulation of both HIF-1␣ and HIF-2␣ subunits and that the contribution of each PHD under particular culture conditions is strongly dependent on the abundance of the enzyme. Thus in different cell types, isoform-specific patterns of PHD induction by hypoxia and estrogen alter both the relative abundance of the PHDs and their relative contribution to the regulation of HIF. In addition, the PHDs manifest specificity for different prolyl hydroxylation sites within each HIF-␣ subunit, and a degree of selectively between HIF-1␣ and HIF-2␣ isoforms, indicating that differential PHD inhibition has the potential to selectively alter the characteristics of HIF activation.

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Section: Phd Isoforms 1-3 Contribute To the Regulation Of Hif-1␣ Undementioning

confidence: 85%

Section: Phd Isoforms Manifest Distinct Patterns Of Cellular Expression-mentioning

confidence: 99%

Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor

Appelhoff

Tian

Raval

et al. 2004

Journal of Biological Chemistry

966

914

View full text Add to dashboard Cite

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“…Determination of ER␣ target genes has recently been undertaken by using DNA microarrays, identifying hundreds of genes with altered expression upon E 2 treatment of human breast cancer cells (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). However, while providing information of the global action of E 2 in these cells, gene expression profiling can rarely discriminate between direct and indirect ER␣ targets.…”

mentioning

confidence: 99%

Location analysis of estrogen receptor α target promoters reveals that FOXA1 defines a domain of the estrogen response

Laganière

Deblois

Lefèbvre

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

341

315

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Nuclear receptors can activate diverse biological pathways within a target cell in response to their cognate ligands, but how this compartmentalization is achieved at the level of gene regulation is poorly understood. We used a genome-wide analysis of promoter occupancy by the estrogen receptor ␣ (ER␣) in MCF-7 cells to investigate the molecular mechanisms underlying the action of 17␤-estradiol (E2) in controlling the growth of breast cancer cells. We identified 153 promoters bound by ER␣ in the presence of E2. Motif-finding algorithms demonstrated that the estrogen response element (ERE) is the most common motif present in these promoters whereas conventional chromatin immunoprecipitation assays showed E2-modulated recruitment of coactivator AIB1 and RNA polymerase II at these loci. The promoters were linked to known ER␣ targets but also to many genes not directly associated with the estrogenic response, including the transcriptional factor FOXA1, whose expression correlates with the presence of ER␣ in breast tumors. We found that ablation of FOXA1 expression in MCF-7 cells suppressed ER␣ binding to the prototypic TFF1 promoter (which contains a FOXA1 binding site), hindered the induction of TFF1 expression by E2, and prevented hormone-induced reentry into the cell cycle. Taken together, these results define a paradigm for estrogen action in breast cancer cells and suggest that regulation of gene expression by nuclear receptors can be compartmentalized into unique transcriptional domains by means of licensing of their activity to cofactors such as FOXA1.ChIP-on-chip ͉ forkhead box ͉ transcription ͉ cell cycle E stradiol (17␤-estradiol, E 2 ) is a potent growth factor of human breast cancer cells that exerts its action mainly through estrogen receptor ␣ (NR3A1, ER␣), a member of the superfamily of nuclear receptors (1). Despite significant advancement into our understanding of the molecular mechanisms of ER␣ action (2), little is known about mediators of the estrogen pathway that assist in the initiation, compartmentalization, and propagation of its signal at the level of gene expression. Delineation of how ER␣ induces precise biological responses in breast cancer cells and other cell types has clearly been limited by the lack of data on the transcriptional regulatory regions of ER␣ direct target genes.ER␣ regulates the expression of target genes by binding to specific sites in the chromatin, referred to as estrogen response elements (EREs) (3), or by interacting with other transcription factors bound to their own specific recognition sites (4-6). Determination of ER␣ target genes has recently been undertaken by using DNA microarrays, identifying hundreds of genes with altered expression upon E 2 treatment of human breast cancer cells (7-17). However, while providing information of the global action of E 2 in these cells, gene expression profiling can rarely discriminate between direct and indirect ER␣ targets. In addition, bioinformatic and comparative genomics have also been used successfully to identify high-...

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“…Interestingly, the EGL-9 domain that was reported to be the active domain in regulating HIF-1a is conserved in Falkor, which seems to be the mouse ortholog of human PHD1, suggesting that Falkor might have a similar role in mouse cells. In yet another study, PHD1, the human homolog of Falkor was cloned by SAGE as an estrogen-induced gene in a breast cancer cell line and was designated EIT-6 (Seth et al, 2002). In this study, EIT-6 was found to promote colony growth in a human breast cancer cell line.…”

Section: Discussionmentioning

confidence: 81%

“…During the course of this study, the human homologs of Falkor, SM-20, and a third family member were cloned by several groups, creating a conserved family of mouse and human proteins (Bruick and McKnight, 2001;Epstein et al, 2001;Seth et al, 2002;Taylor, 2001). …”

Section: Cloning Of Falkormentioning

confidence: 99%

Falkor, a novel cell growth regulator isolated by a functional genetic screen

et al. 2002

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A novel cell growth regulator, named Falkor, was identified using a functional approach to mammalian gene cloning, the Genetic Supressor Elements (GSE) method. In this screen, expression of the C-terminal domain of Falkor conferred cells with resistance to cisplatin-induced growth arrest. Expression of the Cterminus of Falkor, but not of the full-length protein, enhanced cell growth both following genotoxic stress and under normal conditions suggesting a general role for this protein in cell growth control. This effect of the Cterminus fragment was abrogated by over-expression of the full-length Falkor, suggesting that the fragment counteracts the function of the full-length protein. Falkor is encoded by a 2-kb mRNA which is present at different levels in various tissues, and is localized in the nucleus of cells. The C-terminal domain of Falkor, isolated from the GSE library, has significant homology to a known human and rat cell growth regulator, SM-20, and to the C. elegans protein EGL-9, recently shown to modify the Hypoxia Inducible Factor-1a. The homology suggests that these proteins share a functional domain that is conserved among a family of growth regulation proteins.

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Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression)

Cited by 102 publications

References 34 publications

Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor

Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor

Location analysis of estrogen receptor α target promoters reveals that FOXA1 defines a domain of the estrogen response

Falkor, a novel cell growth regulator isolated by a functional genetic screen

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