Transcriptional Activation of the Nuclear Receptor Corepressor RIP140 by Retinoic Acid: A Potential Negative-Feedback Regulatory Mechanism

Kerley, Joanna S.; Olsen, Shannon L; Freemantle, Sarah J.; Spinella, Michael J.

doi:10.1006/bbrc.2001.5274

Cited by 57 publications

(64 citation statements)

References 32 publications

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“…1A). Furthermore, these cells respond to tRA, as assessed by the RAR controlled RIP140 gene expression ( [17]; and results not shown). However, although RA signaling pathway is intact, MDA-MB-231 cells do not express NIS in response to either tRA or any other ligand known to induce NIS in other cell systems ( [3]; and data not shown).…”

Section: Ectopic Era Expression In Mda-mb-231 Upregulates Nis Expressionmentioning

confidence: 99%

Unliganded estrogen receptor-α activates transcription of the mammary gland Na+/I− symporter gene

Alotaibi¹,

Yaman²,

Demirpençe³

et al. 2006

Biochemical and Biophysical Research Communications

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The function of sodium iodide symporter (Na + /I À symporter, or NIS) in mammary epithelial cells is essential for the accumulation of I À in milk; the newborn's first source of I À for thyroid hormone synthesis. Furthermore, increased mammary gland NIS expression has previously been shown in human breast cancer. Several hormones and factors including all-trans-retinoic acid (tRA) regulate the expression of NIS. In this study, using breast cancer cell lines, we established that tRA-responsive NIS expression is confined to estrogen receptor-a (ERa) positive cells and we investigated the role of ERa in the regulation of NIS expression. We showed that the suppression of endogenous ERa by RNA interference downregulates NIS expression in ERa positive mammary cells. Besides, in an ERa negative cell line, reintroduction of ERa resulted in the expression of NIS in a ligand-independent manner. We also identified a novel estrogen-responsive element in the promoter region of NIS that specifically binds ERa and mediates ERa-dependent activation of transcription. Our results indicate that unliganded ERa (apo-ERa) contributes to the regulation of NIS gene expression. In mammary gland lactocytes, sodium/iodide (Na + /I À ) symport via NIS is required to secrete I À in mother's milk [1]. I À in milk is used by the newborn in thyroid hormone biosynthesis, and thus it plays an essential role in post-natal development of skeletal muscles, nervous system, and lungs [2]. In vivo experiments in mice have previously demonstrated that in normal physiology, NIS expression is strictly linked to mammary development in gestation, and to lactation [1]. Non-lactating mammary gland tissue in female mice does not express NIS unless animals receive subcutaneous oxytocin treatments for three consecutive days. On the other hand, a similar treatment in ovariectomized mice is not sufficient for NIS upregulation. In these surgically treated animals, administration of 17-b-estradiol (E2) together with oxytocin is essential for functional expression of NIS. The fact that E2 treatment was only essential in ovariectomized animals, whereas lactogenic hormones were sufficient for functional NIS expression in surgically untreated mice, suggested that ovary functions and endogenous estrogens are essential in upregulating NIS expression [1]. Unlike in non-lactating mammary gland tissue, in transgenic mice bearing experimental breast cancers triggered by Erb-B2/neu and ras oncogenes, functional expression of NIS significantly increases [1]. In the same study, human breast cancer specimens were also analyzed, and an increased NIS expression was detected in human invasive breast cancer and ductal carcinoma in situ, as compared to no expression of NIS in healthy breast samples obtained from reductive mammoplasty operations [1].Recent studies with an ERa+ mammary cell line model, MCF-7, have led to the identification of additional hormones or ligands that control transcriptional regulation of NIS. In this cell line, the symporter gene was shown to be indu...

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Section: Ectopic Era Expression In Mda-mb-231 Upregulates Nis Expressionmentioning

confidence: 99%

Unliganded estrogen receptor-α activates transcription of the mammary gland Na+/I− symporter gene

Alotaibi¹,

Yaman²,

Demirpençe³

et al. 2006

Biochemical and Biophysical Research Communications

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“…For Northern analysis, total RNA was isolated using TriReagent (Invitrogen). Northern hybridizations were performed as described previously (24). The RIP140 probe was a radiolabeled BglII/XhoI 1-kb fragment from plasmid pSG5-HAhRIP140 (22).…”

Section: Methodsmentioning

confidence: 99%

Limiting Effects of RIP140 in Estrogen Signaling

White¹,

Yore

Deng

et al. 2005

Journal of Biological Chemistry

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The receptor interacting protein 140 (RIP140) belongs to a unique subclass of nuclear receptor coregulators with the ability to bind and repress the action of a number of agonist-bound hormone receptors. We have previously demonstrated that all-trans-retinoic acid (RA) induction of RIP140 constitutes a rate-limiting step in the regulation of retinoid receptor signaling. Here we demonstrate that RIP140 is also a limiting regulator of estrogen receptor signaling. Overexpression of RIP140 dose dependently inhibits estrogen-dependent reporter activity in human breast cancer cells. Furthermore, small interfering RNA to RIP140 enhances estrogen-dependent signaling. Our previous studies indicate that RIP140 is a direct target of RA. We report here that RA can abrogate estrogen-mediated cell cycle re-entry. In addition, RA treatment of estrogen-dependent breast cancer cells opposes estrogen receptor-dependent reporter activity, implying that a proportion of RA effects are anti-estrogenic. We provide evidence for a role for RIP140 in mediating anti-estrogenic effects of RA. RIP140 small interfering RNA blocks RA-mediated repression of estrogen receptor activity and provides a growth advantage to estrogen-dependent cells. Together these data implicate a regulatory role for RIP140 in mediating anti-estrogenic effects of RA in estrogendependent breast cancer cells and suggest that acute regulation of coregulator expression may be a general mechanism to integrate diverse hormone signals.

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“…Retinoid induction of RIP140 could provide a negative feedback on gene expression mediated by ligand-activated retinoid receptors. 97 The use of retinoids in cancer chemoprevention led to the development of a human bronchial epithelial chemoprevention model. 98 Immortalized human bronchial epithelial cells were malignantly transformed after independent exposure to the tobacco-derived carcinogens: N-nitrosamine-4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK) or cigarette smoke condensate (CSC).…”

Section: Spotlightmentioning

confidence: 99%