Expression of Estrogen Receptor Coactivators in the Rat Uterus1

Nephew, Kenneth P.; Ray, Shahla; Hlaing, Myint; Ahluwalia, Amrita; Wu, Simon D.; Long, Xinghua; Hyder, Salman M.; Bigsby, Robert M.

doi:10.1095/biolreprod63.2.361

Cited by 41 publications

(30 citation statements)

References 38 publications

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“…This is in agreement with other studies in which estradiol treatment did not regulate the expression of TIF1a, AIB1, SMRT or SRC-1 in MCF-7 cells (52) or SRC-1, glucocorticocoid receptor-interacting protein-1, AIB1, receptor-interacting protein-140 or p300 in the rat uterus (63). Yet there is evidence that some cofactors are regulated by estradiol.…”

Section: Discussionsupporting

confidence: 93%

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: Discussionsupporting

confidence: 93%

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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“…In contrast, SRC-1 mRNA levels have been reported to be insensitive to E 2 in the uterus of the rat. SMRT mRNA expression is reported to be low and unchanged after secretagogue stimulation (Nephew et al 2000). In this study, we found low levels of SRC-1 mRNA in untreated cells; however, in the presence of forskolin or AII, SRC-1 mRNA levels were increased.…”

Section: Discussionsupporting

confidence: 48%

Coregulatory protein–orphan nuclear receptor interactions in the human adrenal cortex

Kelly

McKenna²,

Young

2005

Journal of Endocrinology

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The capacity of the adrenal to produce steroids is controlled in part through the transcriptional regulation of steroid enzymes. The orphan nuclear receptor steroidogenic factor 1 (SF-1) is central to the transcriptional regulation of all steroid hydroxylase enzymes, whereas nur77 can preferentially regulate steroid enzyme genes relevant to cortisol production. We hypothesised that, in the presence of secretagogues, SF-1 and nur77 may differentially interact with coregulatory proteins in the human adrenal cortex. Both coregulatory proteins, steroid receptor coactivator (SRC-1) and silencing mediator for retinoid and thyroid hormones (SMRT), were found to be expressed in the zona fasciculata and reticularis in the human adrenal cortex, but were largely absent from the zona glomerulosa. Both coregulatory proteins were colocalised with SF-1 and nur77. In the H295R adrenal tumour cell line, SF-1 and nur77 transcripts were increased in cells in the presence of forskolin, whereas nur77 mRNA was also induced with angiotensin II (AII). The coactivator SRC-1 mRNA was increased in the presence of both forskolin and AII. Forskolin induced recruitment of SRC-1 to the SF-1 response element and induced SRC-1-SF-1 interactions, whereas AII increased recruitment of SRC-1 to the nur77 response element and induced SRC-1-nur77 interactions. The corepressor SMRT interacted with SF-1 in the presence of AII and with nur77 in cells treated with forskolin. Orphan nuclear receptor-coregulatory protein interactions may have consequences for the regulation of key steroidogenic enzymes in the human adrenal cortex.

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“…Although studies had reported SRC-2 expression in the human and rodent female reproductive tract (11,28,29,33,42,47), a more comprehensive immunohistochemical study was required to determine whether P-responsive cell lineages within reproductive tissues of the cycling mouse express SRC-2. Nuclear SRC-2 immunoreactivity was detected in the uterine epithelium (luminal and glandular compartments), as well as throughout the underlying stroma and myometrium ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Steroid Receptor Coactivator 2 Is Critical for Progesterone-Dependent Uterine Function and Mammary Morphogenesis in the Mouse

Mukherjee

Soyal

Fernández-Valdivia

et al. 2006

Molecular and Cellular Biology

106

145

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Although the essential involvement of the progesterone receptor (PR) in female reproductive tissues is firmly established, the coregulators preferentially enlisted by PR to mediate its physiological effects have yet to be fully delineated. To further dissect the roles of members of the steroid receptor coactivator (SRC)/p160 family in PR-mediated reproductive processes in vivo, state-of-the-art cre-loxP engineering strategies were employed to generate a mouse model (PR Cre/؉ SRC-2 flox/flox ) in which SRC-2 function was abrogated only in cell lineages that express the PR. Fertility tests revealed that while ovarian activity was normal, PR Cre/؉ SRC-2 flox/flox mouse uterine function was severely compromised. Absence of SRC-2 in PR-positive uterine cells was shown to contribute to an early block in embryo implantation, a phenotype not shared by SRC-1 or -3 knockout mice. In addition, histological and molecular analyses revealed an inability of the PR Cre/؉ SRC-2 flox/flox mouse uterus to undergo the necessary cellular and molecular changes that precede complete P-induced decidual progression. Moreover, removal of SRC-1 in the PR Cre/؉ SRC-2 flox/flox mouse uterus resulted in the absence of a decidual response, confirming that uterine SRC-2 and -1 cooperate in P-initiated transcriptional programs which lead to full decidualization. In the case of the mammary gland, whole-mount and histological analysis disclosed the absence of significant ductal side branching and alveologenesis in the hormone-treated PR Cre/؉ SRC-2flox/flox mammary gland, reinforcing an important role for SRC-2 in cellular proliferative changes that require PR. We conclude that SRC-2 is appropriated by PR in a subset of transcriptional cascades obligate for normal uterine and mammary morphogenesis and function.The progesterone (P) receptor (PR) knockout (KO) mouse, in which both isoforms (PR-A and -B) were ablated, highlighted the importance of P as a pleiotropic coordinator of female reproductive biology (24). Abrogation of PR not only undermined uterine morphogenesis and function but also severely compromised the normal operation of the hypothalamopituitary-ovarian axis. These studies further revealed a crucial role for P signaling in mammary epithelial proliferation, an essential cellular event that enables parity-induced mammary morphogenesis to manifest in the adult. In addition, the PR KO mouse exhibited a marked reduction in mammary tumor susceptibility (25), revealing a dual role for PR-mediated epithelial proliferation in mammary tumorigenesis, as well as in normal mammary morphogenesis.Apart from providing new cellular principles by which P influences proliferative and differentiative programs obligate for target tissue morphogenesis and tumorigenesis, two important questions have emerged from these studies regarding PR's mechanism of action for a given target tissue: (i) what are the signature molecular effectors that transduce the P signal to an appropriate physiological response, and (ii) which coregulators (coactivators and/or corep...

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Expression of Estrogen Receptor Coactivators in the Rat Uterus1

Cited by 41 publications

References 38 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

Coregulatory protein–orphan nuclear receptor interactions in the human adrenal cortex

Steroid Receptor Coactivator 2 Is Critical for Progesterone-Dependent Uterine Function and Mammary Morphogenesis in the Mouse

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