Id-1 is not expressed in the luminal epithelial cells of mammary glands

Uehara, Norihisa; Chou, Yu Chien; Galvez, Jose J.; Candia, Paola de; Cardiff, Robert D.; Benezra, Robert; Shyamala, G.

doi:10.1186/bcr560

Cited by 18 publications

(13 citation statements)

References 11 publications

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“…However, the same staining pattern was seen in Id1 null lungs, indicating that ID1 staining of pulmonary VSMCs using this antibody is unreliable. This negative finding is of importance, since a number of studies have used this antibody to identify the cellular localization of ID1 in a variety of different tissues, including the lung (1,3,4,6,8,10,17,18,30,41,44,47,52). Id2 null mice were not available for these studies, so our analyses of ID2 regulation and localization have to be interpreted with caution.…”

Section: Discussionmentioning

confidence: 99%

“…We first evaluated the specificity of three different commercially available ID1 antibodies by comparing staining of lung sections from wild-type and Id1 null mice exposed to 1-wk hypoxia. The first antibody we tested, a rabbit polyclonal anti-ID1 antibody from Santa Cruz (C-20, SC-488), has been used extensively to evaluate ID1 expression domains in a variety of different tissues (1,3,4,6,8,10,17,18,30,41,44,47,52). This antibody gave weak but selective staining of pulmonary ECs in wild-type but not Id1 null mice (Supplemental Fig.…”

Section: Regulation Of Pulmonary Id1-3 Expression Levels By Hypoxiamentioning

confidence: 99%

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ID family protein expression and regulation in hypoxic pulmonary hypertension

Lowery¹,

Frump²,

Anderson

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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To address this, we evaluated pulmonary expression of ID proteins in a mouse model of hypoxia-induced PH. There is selective induction of ID1 and ID3 expression in hypoxic pulmonary vascular smooth muscle cells (VSMCs) in vivo, and ID1 and ID3 expression are increased by hypoxia in cultured pulmonary VSMCs in a BMPdependent fashion. ID4 protein is barely detectable in the mouse lung, and while ID2 is induced in hypoxic peripheral VSMCs in vivo, it is not increased by hypoxia or BMP signaling in cultured pulmonary VSMCs. In addition, the PH response to chronic hypoxia is indistinguishable between wild type and Id1 null mice. This is associated with a compensatory increase in ID3 but not ID2 expression in pulmonary VSMCs of Id1 null mice. These findings indicate that ID1 is dispensable for mounting a normal pulmonary vascular response to hypoxia, but suggest that ID3 may compensate for loss of ID1 expression in pulmonary VSMCs. Taken together, these findings indicate that ID1 and ID3 expression are regulated in a BMP-dependent fashion in hypoxic pulmonary VSMCs, and that ID1 and ID3 may play a cooperative role in regulating BMP-dependent VSMC responses to chronic hypoxia. hypoxia; bone morphogenetic protein signaling; ID1; ID2; ID3; vascular smooth muscle cells; endothelial cells GENETIC STUDIES IN PATIENTS with hereditary pulmonary arterial hypertension (HPAH) indicate that defective bone morphogenetic protein (BMP) type 2 receptor (BMPR2) signaling plays a critical role in promoting pulmonary hypertension (PH) and obliterative pulmonary vascular remodeling in this disease (16,25). Studies in mice carrying heterozygous null and hypomorphic germ line Bmpr2 mutations show that these mice do not develop spontaneous PH, but they have increased susceptibility to PH in response to inflammatory mediators and serotonin (22,38,39) or to chronic hypoxia (9). Conditional deletion of Bmpr2 in endothelial cells (ECs) promotes spontaneous PH in a subset of affected mice (11), indicating that defective BMPR2 signaling plays a role in regulating EC function. However, interference with BMPR2 signaling in vascular smooth muscle cells (VSMCs) by overexpression of a dominant negative BMPR2 mutation also promotes spontaneous PH in mice (45). Furthermore, conditional deletion of the BMP type 1 receptor ALK3 in VSMCs reduces hypoxic pulmonary vascular remodeling and VSMC proliferation (7). These findings indicate that defective BMPR2 signaling influences both the EC and VSMC compartments in the pulmonary vasculature. However, the relationship between defective BMP signaling and vascular cell phenotypes in HPAH is complex and poorly understood (23).One approach to explore this has been to investigate the downstream signaling pathways that mediate the effects of BMP receptor mutations in different pulmonary vascular cell types. These studies also enable us to interrogate PH-associated alterations in BMP signaling that occur in the pulmonary vasculature in the absence of BMPR2 mutations. Activation of the BMP receptors leads to COOH-termi...

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Section: Discussionmentioning

confidence: 99%

Section: Regulation Of Pulmonary Id1-3 Expression Levels By Hypoxiamentioning

confidence: 99%

ID family protein expression and regulation in hypoxic pulmonary hypertension

Lowery¹,

Frump²,

Anderson

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In the mammary gland, ID1 is not detectable in luminal epithelium during any phase of development (Uehara et al, 2003;Nair et al, 2010). Id2 is expressed in mammary epithelial cells and is important for terminal differentiation in cultured mammary epithelial cells and for mammary gland alveologenesis during pregnancy (Mori et al, 2000;Parrinello et al, 2001;Itahana et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

ID4 regulates mammary gland development by suppressing p38MAPK activity

et al. 2011

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SUMMARYThe ID family of helix-loop-helix proteins regulates cell proliferation and differentiation in many different developmental pathways, but the functions of ID4 in mammary development are unknown. We report that mouse Id4 is expressed in cap cells, basal cells and in a subset of luminal epithelial cells, and that its targeted deletion impairs ductal expansion and branching morphogenesis as well as cell proliferation induced by estrogen and/or progesterone. We discover that p38MAPK is activated in Id4-null mammary cells. p38MAPK is also activated following siRNA-mediated Id4 knockdown in transformed mammary cells. This p38MAPK activation is required for the reduced proliferation and increased apoptosis in Id4-ablated mammary glands. Therefore, ID4 promotes mammary gland development by suppressing p38MAPK activity.KEY WORDS: ID4, p38MAPK (MAPK14, MAPK11), Mammary development, Breast cancer, Wnt, Mouse ID4 regulates mammary gland development by suppressing p38MAPK activity

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“…There are conflicting reports on whether Id1 is expressed in the epithelial (2,4,11,35) or endothelial (14,19,36) cells within the mammary gland. We were able to reliably detect Id1 mRNA and protein expression in a range of normal and immortalized human mammary epithelial cells by Western blotting, reverse transcription-PCR, or immunofluorescence (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

The Helix-Loop-Helix Protein Id1 Requires Cyclin D1 to Promote the Proliferation of Mammary Epithelial Cell Acini

et al. 2008

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Overexpression of the helix-loop-helix (HLH) protein Id1 has been associated with metastasis in breast cancer, but its role in models of early breast tumorigenesis is not well characterized. We show that the down-regulation of endogenous Id1 via proteosomal degradation and relocalization from the nucleus to the cytoplasm is an early event in the formation of mammary epithelial acini. Overexpression of Id1 in both human MCF-10A and primary mouse mammary epithelial cells disrupted normal acinar development by increasing acinar volume. This occurred in an HLH domain-dependent fashion via an increase in S phase. Id1 overexpression also increased apoptosis leading to accelerated luminal clearance, and this was reversed by coexpression of the proto-oncogene Bcl2, leading to large, disorganized structures with filled lumina. Id1 overexpression was unable to increase the volume of cyclin D1 À/À acini, indicating that Id1 is dependent on cyclin D1 for its proliferative effects. In summary, Id1 may contribute to early breast cancer by promoting excessive proliferation through cyclin D1. [Cancer Res 2008;68(8):3026-36]

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Id-1 is not expressed in the luminal epithelial cells of mammary glands

Cited by 18 publications

References 11 publications

ID family protein expression and regulation in hypoxic pulmonary hypertension

ID family protein expression and regulation in hypoxic pulmonary hypertension

ID4 regulates mammary gland development by suppressing p38MAPK activity

The Helix-Loop-Helix Protein Id1 Requires Cyclin D1 to Promote the Proliferation of Mammary Epithelial Cell Acini

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