Expression and Hormonal Regulation of Coactivator and Corepressor Genes

Misiti, Silvia; Schomburg, Lutz; Yen, Paul M.; Chin, William W.

doi:10.1210/endo.139.5.5971

Cited by 166 publications

(109 citation statements)

References 41 publications

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“…In MCF-7 cells RIP140 mRNA expression was increased by estradiol (52). The regulation of SRC-1 and SMRT by estradiol has also been shown in the rat pituitary (64). In addition, other NR ligands have been shown to regulate cofactors.…”

Section: Discussionmentioning

confidence: 86%

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Regulation of nuclear receptor and cofactor expression in breast cancer cell lines

Vienonen

Miettinen

Manninen

et al. 2003

European Journal of Endocrinology

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Objective: The aim of this study was to compare the expression profile of nuclear receptors (NRs) and cofactors in different breast cancer cell lines as well as their regulation by estradiol, insulin and progestin R5020. Methods: Expression of NRs and cofactors were determined from MCF-7, T-47D and ZR-75-1 breast cancer cell lines. Multiprobe ribonuclease protection assay and real-time RT-PCR were used to quantitate mRNA levels of steroid receptors, vitamin D receptors (VDR) and retinoic acid receptors (RAR) and cofactors: amplified in breast cancer-1, cyclic AMP response element binding protein (CBP), p300/CBP-associated factor, p300, nuclear receptor corepressor and silencing mediator of repressed transcription. Results: Basal expression levels of NRs and cofactors varied depending on the cell line. Cell line-specific regulation of androgen receptor, estrogen receptor-a (ERa), RARa, RARg and VDR expression was observed after estradiol treatment. Likewise, differences in the regulation of ERa, RARa and VDR expression after R5020 treatment were observed. We did not observe significant regulation of cofactor expression after estradiol, insulin or progestin treatment in any cell line analyzed. Conclusions:The results showed that not only is the expression profile of the NRs and cofactors cell line specific but also the regulation of NR expression. Thus the determinants of the ligand action (receptor and cofactor expression) varied considerably among different cell clones of the breast cancer cells. This suggested a gradient of NR-ligand sensitivities in the hormone-dependent breast cancers, which produces an additional challenge in developing novel ligands for hormone replacement therapy and breast cancer treatment.

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Section: Discussionmentioning

confidence: 86%

“…For example, all-trans retinoic acid treatment increased AIB1 expression in HL-60 cells (65) and SMRT expression in neuroblastoma cell lines (66). Thyroid hormone treatment slightly increased SRC-1 expression in the rat pituitary (64). However, whether progestins regulate cofactor expression has not been studied earlier.…”

Section: Discussionmentioning

confidence: 99%

Regulation of nuclear receptor and cofactor expression in breast cancer cell lines

Vienonen

Miettinen

Manninen

et al. 2003

European Journal of Endocrinology

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“…Similar observations have been made for other coregulatory molecules. For example, SRC-1 is downregulated by dexamethasone (Kurihara et al, 2000) and oestrogen (Misiti et al, 1998). RIP140 corepressor expression is increased 2-3 fold by 17b-oestradiol in MCF7 breast cancer cells, while antioestrogens had the opposite effect (Thenot et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Expression of Tip60, an androgen receptor coactivator, and its role in prostate cancer development

et al. 2003

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“…Another possible explanation for the relative resistance to E action in trabecular bone in female but not male SRC-1 KO mice may be that there is a gender-related difference in SRC-1 steady state mRNA levels in bone [21] or even in SRC-1 protein activity. Significant gender-and sitespecific differences in the expression of SRC-1 in the brain and pituitary gland under basal conditions and following acute stress have previously been noted in rats by Northern blot analysis [22].…”

Section: Discussionmentioning

confidence: 99%

The skeletal response to estrogen is impaired in female but not in male steroid receptor coactivator (SRC)-1 knock out mice

Mödder

Sanyal

et al. 2008

Bone

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Estrogen (E) is critical for the maintenance of bone mass in both female and male mice and steroid receptor coactivator (SRC)-1 has been shown to be important for mediating E effects on bone, at least in female mice. In the present study, we defined the skeletal phenotype of male SRC-1 knock out (KO) mice and compared it with their female littermates. Further, to determine the role of SRC-1 in mediating effects of E on bone in male mice, we examined the skeletal effects of gonadectomy (gnx) with or without E replacement in male mice and placed these findings in the context of our previous studies in female SRC-1 KO mice.Analysis of a large group of male (WT, n=67; SRC-1 KO, n=56) and female (WT, n=66; SRC-1 KO, n=70) mice showed a significant decrease in trabecular volumetric bone mineral density (vBMD) in SRC-1 KO mice compared to their WT littermates in both genders (male SRC-1 KO, 275 ± 3 vs WT, 295 ± 3 mg/cm 3 , P<0.001; female SRC-1 KO, 210 ± 2 vs WT, 221 ± 2 mg/cm 3 , P<0.001). Following gnx and E replacement (10 μg/kg/d), we previously demonstrated that SRC-1 KO female mice have a defect in E action in trabecular, but not in cortical bone. In contrast, we now demonstrate that the same dose of E administered to gnx'd male SRC-1 KO mice was sufficient to prevent trabecular bone loss in these mice. For example, in WT female mice, gnx followed by E replacement maintained spine BMD (1.2 ± 3.4% vs baseline) as compared to gnx without E replacement (−12.7 ± 2.6%, P<0.001 vs sham); this effect of E was absent in SRC-1 KO female mice. By contrast, the identical dose of E was equally effective in maintaining spine BMD in E-treated gnx'd male WT (−5.2 ± 5.1% vs baseline) and male SRC-1 KO (−5.4 ± 5.3%) mice, respectively, as compared to gnx'd mice without E treatment (WT, −17.6 ± 2.5%, P=0.02; SRC-1 KO, −28.6 ± 2.6%, P<0.001 vs sham). E treatment was effective in suppressing cancellous bone turnover in both gnx'd WT and SRC-1 KO male mice as determined by significant reductions in osteoblast and osteoclast numbers; however, in female mice, E treatment only suppressed bone turnover in WT but not in SRC-1 KO mice.Collectively, these findings demonstrate that loss of SRC-1 results in trabecular osteopenia in male and female mice, but in contrast to female mice, this is not due to any detectable resistance to E action in trabecular bone in male SRC-1 KO mice.

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Expression and Hormonal Regulation of Coactivator and Corepressor Genes

Cited by 166 publications

References 41 publications

Regulation of nuclear receptor and cofactor expression in breast cancer cell lines

Regulation of nuclear receptor and cofactor expression in breast cancer cell lines

Expression of Tip60, an androgen receptor coactivator, and its role in prostate cancer development

The skeletal response to estrogen is impaired in female but not in male steroid receptor coactivator (SRC)-1 knock out mice

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