The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals
Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in brea...
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| Format: | Online |
| Language: | English |
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Company of Biologists
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583043/ |
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pubmed-3583043 |
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pubmed-35830432013-03-15 The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals Nautiyal, Jaya Steel, Jennifer H. Mane, Meritxell Rosell Oduwole, Olayiwola Poliandri, Ariel Alexi, Xanthippi Wood, Nicholas Poutanen, Matti Zwart, Wilbert Stingl, John Parker, Malcolm G. Research Articles Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development. Company of Biologists 2013-03-01 /pmc/articles/PMC3583043/ /pubmed/23404106 http://dx.doi.org/10.1242/dev.085720 Text en © 2013. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by-nc-sa/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Nautiyal, Jaya Steel, Jennifer H. Mane, Meritxell Rosell Oduwole, Olayiwola Poliandri, Ariel Alexi, Xanthippi Wood, Nicholas Poutanen, Matti Zwart, Wilbert Stingl, John Parker, Malcolm G. |
| spellingShingle |
Nautiyal, Jaya Steel, Jennifer H. Mane, Meritxell Rosell Oduwole, Olayiwola Poliandri, Ariel Alexi, Xanthippi Wood, Nicholas Poutanen, Matti Zwart, Wilbert Stingl, John Parker, Malcolm G. The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals |
| author_facet |
Nautiyal, Jaya Steel, Jennifer H. Mane, Meritxell Rosell Oduwole, Olayiwola Poliandri, Ariel Alexi, Xanthippi Wood, Nicholas Poutanen, Matti Zwart, Wilbert Stingl, John Parker, Malcolm G. |
| author_sort |
Nautiyal, Jaya |
| title |
The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals |
| title_short |
The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals |
| title_full |
The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals |
| title_fullStr |
The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals |
| title_full_unstemmed |
The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals |
| title_sort |
transcriptional co-factor rip140 regulates mammary gland development by promoting the generation of key mitogenic signals |
| description |
Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development. |
| publisher |
Company of Biologists |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583043/ |
| _version_ |
1611957782851878912 |