Expression of estrogen receptor coregulators in normal and malignant human endometrium

Kershah, Sharif; Desouki, Mohamed Mokhtar; Koterba, Kristen L.; Rowan, Brian G.

doi:10.1016/j.ygyno.2003.10.007

Cited by 58 publications

(41 citation statements)

References 146 publications

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“…The ratio between coactivators SRC-1 and SRC-2 and corepressor NCOR1 decreased in malignant tissues. No significant differences were identified between tumor groups regarding NCOR expression, categorized on the basis of such clinical parameters as grades or stages (37). Upregulation of NCOR1 was also observed in breast cancer, however, a low expression of this gene was associated with worse prognosis and serves as a potential predicting factor for tamoxifen treatment in estrogen receptor α-positive breast cancer (38).…”

Section: Discussionmentioning

confidence: 99%

The WWOX tumor suppressor gene in endometrial adenocarcinoma

Płuciennik

Kośla

Wójcik‐Krowiranda

et al. 2013

International Journal of Molecular Medicine

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Abstract. Endometrial cancer is a lethal malignancy, the causes of which remain to be determined. The aim of the present study, carried out on tumor samples from 79 patients, was to evaluate the role of the WWOX tumor suppressor gene in endometrial adenocarcinoma. The expression levels of WWOX and its protein content were assessed in normal endometrium and cancer samples. Quantitative PCR was used to assess the correlation between the expression levels of WWOX and the genes involved in the proliferation (MKI67), apoptosis (BAX, BCL2), signal transduction (EGFR), cell cycle (CCNE1, CCND1), cell adhesion (CDH1) and transcription regulation (TP73, NCOR1). The relationship between loss of hetero zygosity (LOH) and WWOX mRNA levels was also investigated using high resolution melting. Results of the present study demonstrated a positive correlation of WWOX expression with BCL2 and CCND1 and a negative correlation with BAX, CDH1, NCOR1 and BCL2/BAX ratio. The results also showed that loss of heterozygosity at two analyzed loci of the WWOX gene is frequent in patients with endometrial cancer and that WWOX expression levels are lower in tumor samples than in normal tissue. In conclusion, WWOX may be involved in endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

The WWOX tumor suppressor gene in endometrial adenocarcinoma

Płuciennik

Kośla

Wójcik‐Krowiranda

et al. 2013

International Journal of Molecular Medicine

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“…The reverse transcription product was measured by quantitative real-time PCR using the Real-time PCR master mix (Applied Biosystems) in the 7500 Real-Time PCR System (Applied Biosystems). The primers and TaqMan probe for SMRT (Kershah et al, 2004), NCoR (Kershah et al, 2004) or luciferase was purchased from Integrated DNA Technologies Inc. (Coralville, IA, USA). The primers and the TaqMan probe for the human TAFII30 and control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene were purchased from Applied Biosystems.…”

Section: Gene Silencing With Sirnasmentioning

confidence: 99%

Estrogen-induced and TAFII30-mediated gene repression by direct recruitment of the estrogen receptor and co-repressors to the core promoter and its reversal by tamoxifen

et al. 2007

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Estradiol (E 2 ) acts through the estrogen receptor (ER) to downregulate many genes, and tamoxifen (Tam) largely reverses this repression but the underlying mechanisms are unclear. Repression of the folate receptor (FR)-a P4 core promoter by ER is enhanced by E 2 and reversed by Tam. This effect was unaffected by inhibition of new protein synthesis and required the E/F and the DNA-binding domains of ER without direct binding of ER to DNA. The repression by E 2 /ER was not specific for either Sp1 or TATA elements but was loosely selective for the initiator and flanking sequence. Insertion of a response element or a relatively strong Sp1 cluster to recruit ER upstream of the core promoters caused a switch to activation by E 2 /ER that was inhibited by Tam. In nuclear extracts, association of ER with a biotinylated core promoter fragment was promoted by E 2 but Tam blocked this effect. Repression/ de-repression of the P4 promoter and endogenous FR-a expression by E 2 /Tam required SMRT and/or NCoR. ER associated with the chromosomal P4 promoter and SMRT and NCoR associated with it in an ER-dependent manner; these associations were favored by E 2 but disrupted by Tam, in the short term, without changes in ER expression. TAFII30 was required for optimal P4 promoter activity and for the repressive association of ER. E2 may thus maintain a low transcriptional status of genes by favoring direct TAFII30-dependent association of ER with the core promoter in a co-repressor complex containing SMRT and/or NCoR; this repression is overridden in target genes containing an upstream element that strongly recruits ER. In addition to suppressing the activation of classical E2 target genes, Tam may upregulate genes by passively dissociating the ER co-repressor complex.

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“…Crystal structures have shown the binding of NCoR and SMRT to both PR-A and PR-B, but this was in the presence of the selective modulator asoprisnil (Madauss et al, 2007). Overexpression of these corepressor proteins in breast and endometrial cancers has been observed, but their role in cancer development remains unclear (Kurebayashi et al, 2000;Kershah et al, 2004).…”

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confidence: 99%