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Mammary stem cell

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https://www.readbyqxmd.com/read/29241686/rankl-and-rank-from-mammalian-physiology-to-cancer-treatment
#1
REVIEW
Shuan Rao, Shane J F Cronin, Verena Sigl, Josef M Penninger
The tumor necrosis factor (TNF) receptor RANK (TNFRSF11A) and its ligand RANKL (TNFSF11) regulate osteoclast development and bone metabolism. They also control stem cell expansion and proliferation of mammary epithelial cells via the sex hormone progesterone. As such, RANKL and RANK have been implicated in the onset of hormone-induced breast cancer. Recently, RANK/RANKL were identified as crucial regulators for BRCA1 mutation-driven breast cancer. Current prevention strategies for BRCA1 mutation carriers are associated with wide-ranging risks; therefore, the search for alternative, non-invasive strategies is of paramount importance...
December 11, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/29232628/epithelial-plasticity-in-the-mammary-gland
#2
REVIEW
Lindsey Seldin, Armelle Le Guelte, Ian G Macara
Many epithelial tissues rely on multipotent stem cells for the proper development and maintenance of their diverse cell lineages. Nevertheless, the identification of multipotent stem cell populations within the mammary gland has been a point of contention over the past decade. In this review, we provide a critical overview of the various lineage-tracing studies performed to address this issue and conclude that although multipotent stem cells exist in the embryonic mammary placode, the postnatal mammary gland instead contains distinct unipotent progenitor populations that contribute to stage-specific development and homeostasis...
December 9, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29229854/interferon-beta-represses-cancer-stem-cell-properties-in-triple-negative-breast-cancer
#3
Mary R Doherty, HyeonJoo Cheon, Damian J Junk, Shaveta Vinayak, Vinay Varadan, Melinda L Telli, James M Ford, George R Stark, Mark W Jackson
Triple-negative breast cancer (TNBC), the deadliest form of this disease, lacks a targeted therapy. TNBC tumors that fail to respond to chemotherapy are characterized by a repressed IFN/signal transducer and activator of transcription (IFN/STAT) gene signature and are often enriched for cancer stem cells (CSCs). We have found that human mammary epithelial cells that undergo an epithelial-to-mesenchymal transition (EMT) following transformation acquire CSC properties. These mesenchymal/CSCs have a significantly repressed IFN/STAT gene expression signature and an enhanced ability to migrate and form tumor spheres...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29207201/hypoxia-modulates-the-stem-cell-population-and-induces-emt-in-the-mcf-10a-breast-epithelial-cell-line
#4
Carl S Daly, Arwa Flemban, Mai Shafei, Myra E Conway, David Qualtrough, Sarah J Dean
A common feature among pre-malignant lesions is the induction of hypoxia through increased cell propagation and reduced access to blood flow. Hypoxia in breast cancer has been associated with poor patient prognosis, resistance to chemotherapy and increased metastasis. Although hypoxia has been correlated with factors associated with the latter stages of cancer progression, it is not well documented how hypoxia influences cells in the earliest stages of transformation. Using the immortalized MCF-10A breast epithelial cell line, we used hypoxic culture conditions to mimic reduced O2 levels found within early pre-malignant lesions and assessed various cellular parameters...
December 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29200002/metformin-and-melatonin-inhibit-dmba-induced-mammary-tumorigenesis-in-rats-fed-a-high-fat-diet
#5
Bianka Bojková, Karol Kajo, Terézia Kisková, Peter Kubatka, Pavol Žúbor, Peter Solár, Martin Péč, Marián Adamkov
The data from in-vitro and in-vivo studies show that both peroral antidiabetic metformin (MF) and pineal hormone melatonin (MT) inhibit the growth of many cancers, including breast cancer. However, most in-vivo studies used standard-type diet with low fat content. Therefore, in this study, we evaluated the chemopreventive effect of MF and MT in an in-vivo model of breast cancer in rats on a high-fat diet (10% of total fat). Mammary carcinogenesis was induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats...
December 1, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29187406/ptbp3-mediated-regulation-of-zeb1-mrna-stability-promotes-epithelial-mesenchymal-transition-in-breast-cancer
#6
Pingfu Hou, Lin Li, Fang Chen, Yansu Chen, Hui Liu, Jingjing Li, Jin Bai, Junnian Zheng
The RNA polypyrimidine tract binding protein PTBP3 is a little studied paralog of PTBP1 which has oncogenic properties. In this study, we demonstrate that PTBP3 induces epithelial-mesenchymal transition (EMT) in breast tumor cells and promotes their invasive growth and metastasis. Elevated expression of PTBP3 associated significantly with lymph node metastasis, advanced histology grade, TNM stage, and poor 5-year overall survival of patients. In human mammary epithelial cells, PTBP3 overexpression was sufficient to induce EMT and enhance cell migration, invasion, and cancer stem-like cell properties...
November 29, 2017: Cancer Research
https://www.readbyqxmd.com/read/29187405/her2-driven-breast-tumorigenesis-relies-upon-interactions-of-the-estrogen-receptor-with-coactivator-med1
#7
Yongguang Yang, Marissa Leonard, Yijuan Zhang, Dan Zhao, Mahmoud Charif, Shagufta Khan, Jiang Wang, Elyse Lower, Xiaoting Zhang
Studies of the estrogen receptor (ER) coactivator protein MED1 have revealed its specific roles in pubertal mammary gland development and potential contributions to breast tumorigenesis, based on co-amplification of MED1 and HER2 in certain breast cancers. In this study, we generated a mouse model of mammary tumorigenesis harboring the MMTV-HER2 oncogene and mutation of MED1 to evaluate its role in HER2-driven tumorigenesis. MED1 mutation in its ER-interacting LxxLL motifs was sufficient to delay tumor onset and impair tumor growth, metastasis and cancer stem-like cell formation in this model...
November 29, 2017: Cancer Research
https://www.readbyqxmd.com/read/29187227/obesity-reversibly-depletes-the-basal-cell-population-and-enhances-mammary-epithelial-cell-estrogen-receptor-alpha-expression-and-progenitor-activity
#8
Tamara Chamberlin, Joseph V D'Amato, Lisa M Arendt
BACKGROUND: Obesity is correlated with an increased risk for developing postmenopausal breast cancer. Since obesity rates continue to rise worldwide, it is important to understand how the obese microenvironment influences normal mammary tissue to increase breast cancer risk. We hypothesized that obesity increases the proportion of luminal progenitor cells, which are thought to be the cells of origin for the most common types of breast cancer, potentially leading to an increased risk for breast cancer...
November 29, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29162812/role-of-epithelial-to-mesenchymal-transition-associated-genes-in-mammary-gland-regeneration-and-breast-tumorigenesis
#9
Shaheen S Sikandar, Angera H Kuo, Tomer Kalisky, Shang Cai, Maider Zabala, Robert W Hsieh, Neethan A Lobo, Ferenc A Scheeren, Sopheak Sim, Dalong Qian, Frederick M Dirbas, George Somlo, Stephen R Quake, Michael F Clarke
Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts we demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of EMT-associated genes...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158490/long-lived-unipotent-blimp1-positive-luminal-stem-cells-drive-mammary-gland-organogenesis-throughout-adult-life
#10
Salah Elias, Marc A Morgan, Elizabeth K Bikoff, Elizabeth J Robertson
The hierarchical relationships between various stem and progenitor cell subpopulations driving mammary gland morphogenesis and homoeostasis are poorly understood. Conditional inactivation experiments previously demonstrated that expression of the zinc finger transcriptional repressor Blimp1/PRDM1 is essential for the establishment of epithelial cell polarity and functional maturation of alveolar cells. Here we exploit a Prdm1.CreERT2-LacZ reporter allele for lineage tracing experiments. Blimp1 expression marks a rare subpopulation of unipotent luminal stem cells that initially appear in the embryonic mammary gland at around E17...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158396/emt-programs-promote-basal-mammary-stem-cell-and-tumor-initiating-cell-stemness-by-inducing-primary-ciliogenesis-and-hedgehog-signaling
#11
Vincent J Guen, Tony E Chavarria, Cornelia Kröger, Xin Ye, Robert A Weinberg, Jacqueline A Lees
Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain carcinomas depends on a small subset of tumor cells, called "tumor-initiating cells" (TICs), with SC-like properties. Mammary SCs (MaSCs) reside in the basal compartment of the mammary epithelium, and their neoplastic counterparts, mammary TICs (MaTICs), are thought to serve as the TICs for the claudin-low subtype of breast cancer...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29157216/breast-cancer-protection-by-genomic-imprinting-in-close-kin-families
#12
REVIEW
Srdjan Denic, Mukesh M Agarwal
Human inbreeding generally reduces breast cancer risk (BCR). When the parents are biologically related, their infants have a lower birth weight due to smaller body organs. The undersized breasts, because of fewer mammary stem cells, have a lower likelihood of malignant conversion. Fetal growth is regulated by genomically imprinted genes which are in conflict; they promote growth when derived from the father and suppress growth when derived from the mother. The kinship theory explicates that the intensity of conflict between these genes affects growth and therefore the size of the newborn...
November 21, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/29156681/the-histone-demethylase-kdm3a-is-required-for-normal-epithelial-proliferation-ductal-elongation-and-tumor-growth-in-the-mouse-mammary-gland
#13
Li Qin, Yixiang Xu, Xiaobin Yu, Michael J Toneff, Dabing Li, Lan Liao, Jarrod D Martinez, Yi Li, Jianming Xu
Histone modification alters chromatin architecture to regulate gene transcription. KDM3A is a histone demethylase in the JmjC domain-containing protein family. It removes di- and mono- methyl residues from di- or mono-methylated lysine 9 of histone H3 (H3K9me2/me1). Recent studies have shown that Kdm3a plays an important role in self-renewal of embryonic stem cells, spermatogenesis, metabolism, sex determination and tumor angiogenesis. However, its role in mammary gland development and breast carcinogenesis remains unclear...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#14
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109519/network-pharmacology-based-validation-of-tams-cxcl-1-as-key-mediator-of-xiaopi-formula-preventing-breast-cancer-development-and-metastasis
#15
Neng Wang, Yifeng Zheng, Jiangyong Gu, Youli Cai, Shengqi Wang, Fengxue Zhang, Jianping Chen, Honglin Situ, Yi Lin, Zhiyu Wang
Network pharmacology has become a powerful means of understanding the mechanisms underlying the action of Chinese herbs in cancer treatment. This study aims to validate the preventive effects and molecular mechanisms of a clinical prescription XIAOPI formula against breast cancer. In vivo breast cancer xenograft data showed that XIAOPI delayed breast cancer development and efficiently inhibited lung metastasis, accompanied by prolonged survival benefits and decreased cancer stem cell subpopulations. However, similar phenomenon were not observed in a cell model...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29103953/wnt-mediated-regulation-of-foxo1-constitutes-a-critical-axis-maintaining-pubertal-mammary-stem-cell-homeostasis
#16
Amulya Sreekumar, Michael J Toneff, Eajer Toh, Kevin Roarty, Chad J Creighton, George K Belka, Dong-Kee Lee, Jianming Xu, Lewis A Chodosh, JoAnne S Richards, Jeffrey M Rosen
Puberty is characterized by dynamic tissue remodeling in the mammary gland involving ductal elongation, resolution into the mature epithelial bilayer, and lumen formation. To decipher the cellular mechanisms underlying these processes, we studied the fate of putative stem cells, termed cap cells, present in terminal end buds of pubertal mice. Employing a p63(CreERT2)-based lineage-tracing strategy, we identified a unipotent fate for proliferative cap cells that only generated cells with basal features. Furthermore, we observed that dislocated "cap-in-body" cells underwent apoptosis, which aided lumen formation during ductal development...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29066722/bcl-xl-directly-modulates-ras-signalling-to-favour-cancer-cell-stemness
#17
Sophie de Carné Trécesson, Frédérique Souazé, Agnès Basseville, Anne-Charlotte Bernard, Jessie Pécot, Jonathan Lopez, Margaux Bessou, Kristopher A Sarosiek, Anthony Letai, Sophie Barillé-Nion, Isabelle Valo, Olivier Coqueret, Catherine Guette, Mario Campone, Fabien Gautier, Philippe Paul Juin
In tumours, accumulation of chemoresistant cells that express high levels of anti-apoptotic proteins such as BCL-XL is thought to result from the counter selection of sensitive, low expresser clones during progression and/or initial treatment. We herein show that BCL-XL expression is selectively advantageous to cancer cell populations even in the absence of pro-apoptotic pressure. In transformed human mammary epithelial cells BCL-XL favours full activation of signalling downstream of constitutively active RAS with which it interacts in a BH4-dependent manner...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29051494/mir-31-promotes-mammary-stem-cell-expansion-and-breast-tumorigenesis-by-suppressing-wnt-signaling-antagonists
#18
Cong Lv, Fengyin Li, Xiang Li, Yuhua Tian, Yue Zhang, Xiaole Sheng, Yongli Song, Qingyong Meng, Shukai Yuan, Liming Luan, Thomas Andl, Xu Feng, Baowei Jiao, Mingang Xu, Maksim V Plikus, Xing Dai, Christopher Lengner, Wei Cui, Fazheng Ren, Jianwei Shuai, Sarah E Millar, Zhengquan Yu
MicroRNA-mediated post-transcriptional regulation plays key roles in stem cell self-renewal and tumorigenesis. However, the in vivo functions of specific microRNAs in controlling mammary stem cell (MaSC) activity and breast cancer formation remain poorly understood. Here we show that miR-31 is highly expressed in MaSC-enriched mammary basal cell population and in mammary tumors, and is regulated by NF-κB signaling. We demonstrate that miR-31 promotes mammary epithelial proliferation and MaSC expansion at the expense of differentiation in vivo...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29035387/stromal-pten-inhibits-the-expansion-of-mammary-epithelial-stem-cells-through-jagged-1
#19
G M Sizemore, S Balakrishnan, A M Hammer, K A Thies, A J Trimboli, J A Wallace, S T Sizemore, R D Kladney, S A Woelke, L Yu, S A Fernandez, A Chakravarti, G Leone, M C Ostrowski
This corrects the article DOI: 10.1038/onc.2016.383.
October 16, 2017: Oncogene
https://www.readbyqxmd.com/read/29034880/generation-of-induced-pluripotent-stem-cell-ipsc-line-from-a-patient-with-triple-negative-breast-cancer-with-hereditary-exon-17-deletion-of-brca1-gene
#20
Frank Griscelli, Noufissa Oudrhiri, Olivier Feraud, Dominique Divers, Lucie Portier, Ali G Turhan, Annelise Bennaceur Griscelli
BRCA1 germline mutation confers hereditary predisposition for breast and ovarian cancer. To understand the physiopathology of mammary and ovarian epithelial cancer transformation, and to identify early driver molecular events, we have generated an iPSC line from a patient carrying a germline exon 17 deletion in BRCA1 gene (BRAC1Ex17 iPSC) in a high-risk family context. Blood cells were reprogrammed used non-integrative virus of Sendaï. The BRCA1-deleted iPSC had normal karyotype, harboured a deletion in the exon 17 of the BRCA1 gene, expressed pluripotent hallmarks and had the differentiation capacity into the three germ layers...
October 2017: Stem Cell Research
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