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https://www.readbyqxmd.com/read/29035387/stromal-pten-inhibits-the-expansion-of-mammary-epithelial-stem-cells-through-jagged-1
#1
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
#2
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
https://www.readbyqxmd.com/read/29029452/the-h3k27me3-demethylase-kdm6a-is-suppressed-in-breast-cancer-stem-like-cells-and-enables-the-resolution-of-bivalency-during-the-mesenchymal-epithelial-transition
#3
Joseph H Taube, Nathalie Sphyris, Kelsey S Johnson, Keighley N Reisenauer, Taylor A Nesbit, Robiya Joseph, Geraldine V Vijay, Tapasree R Sarkar, Neeraja A Bhangre, Joon Jin Song, Jeffrey T Chang, Min Gyu Lee, Rama Soundararajan, Sendurai A Mani
The deposition of the activating H3K4me3 and repressive H3K27me3 histone modifications within the same promoter, forming a so-called bivalent domain, maintains gene expression in a repressed but transcription-ready state. We recently reported a significantly increased incidence of bivalency following an epithelial-mesenchymal transition (EMT), a process associated with the initiation of the metastatic cascade. The reverse process, known as the mesenchymal-epithelial transition (MET), is necessary for efficient colonization...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28991231/slug-pcad-pathway-controls-epithelial-cell-dynamics-in-mammary-gland-and-breast-carcinoma
#4
Y Idoux-Gillet, M Nassour, E Lakis, F Bonini, C Theillet, S Du Manoir, P Savagner
Mammary gland morphogenesis results from the coordination of proliferation, cohort migration, apoptosis and stem/progenitor cell dynamics. We showed earlier that the transcription repressor Slug is involved in these functions during mammary tubulogenesis. Slug is expressed by a subpopulation of basal epithelial cells, co-expressed with P-cadherin (Pcad). Slug-knockout mammary glands showed excessive branching, similarly to Pcad-knockout. Here, we found that Slug unexpectedly binds and activates Pcad promoter through E-boxes, inducing Pcad expression...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28978719/pharmacological-dual-inhibition-of-tumor-and-tumor-induced-functional-limitations-in-transgenic-model-of-breast-cancer
#5
Ruizhong Wang, Poornima Bhat-Nakshatri, Maria B Padua, Mayuri S Prasad, Manjushree Anjanappa, Max Jacobson, Courtney Finnearty, Victoria Sefcsik, Kyle McElyea, Rachael Redmond, George E Sandusky, Narsimha Penthala, Peter A Crooks, Jianguo Liu, Teresa Zimmers, Harikrishna Nakshatri
Breast cancer progression is associated with systemic effects including functional limitations and sarcopenia without the appearance of overt cachexia. Autocrine/paracrine actions of cytokines/chemokines produced by cancer cells mediate cancer progression and functional limitations. The cytokine-inducible transcription factor NF-κB could be central to this process, as it displays oncogenic functions and is integral to the Pax7:MyoD:Pgc-1β:miR-486 myogenesis axis. We tested this possibility using the MMTV-PyMT transgenic mammary tumor model and the NF-κB inhibitor dimethylaminoparthenolide (DMAPT)...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28976208/pomegranate-extract-alters-breast-cancer-stem-cell-properties-in-association-with-inhibition-of-epithelial-to-mesenchymal-transition
#6
Sameera Nallanthighal, Kristine M Elmaliki, Ramune Reliene
Cancer stem cells (CSCs) have become an important target population in cancer therapy and prevention due to their ability to self-renew, initiate tumors, and resist therapy. We examined whether pomegranate extract (PE) alters characteristics of breast CSCs. Ability to grow as mammospheres is a hallmark of breast CSCs. PE inhibited mammosphere formation in two different cell lines, neoplastic mammary epithelial HMLER and breast cancer Hs578T. In addition, mammosphere-derived cells from PE treatment groups showed reduced mammosphere formation for at least two serial passages...
October 4, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28972074/mechano-signal-transduction-in-mesenchymal-stem-cells-induces-prosaposin-secretion-to-drive-the-proliferation-of-breast-cancer-cells
#7
Seiichiro Ishihara, David R Inman, Wan-Ju Li, Suzanne M Ponik, Patricia Keely
In response to chemical stimuli from cancer cells, mesenchymal stem cells (MSC) can differentiate into cancer-associated fibroblasts (CAF) and promote tumor progression. How mechanical stimuli such as stiffness of the extracellular matrix (ECM) contribute to MSC phenotype in cancer remains poorly understood. Here we show that ECM stiffness leads to mechano-signal transduction in MSC which promotes mammary tumor growth in part through secretion of the signaling protein prosaposin. On a stiff matrix, MSC cultured with conditioned media from mammary cancer cells expressed increased levels of alpha-smooth muscle actin, a marker of CAF, compared to MSC cultured on a soft matrix...
September 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28947532/epithelial-vimentin-plays-a-functional-role-in-mammary-gland-development
#8
Emilia Peuhu, Reetta Virtakoivu, Anja Mai, Anni Wärri, Johanna Ivaska
In the mammary gland, vimentin intermediate filaments are expressed in stromal cells and in basal epithelial cell populations including gland-reconstituting mammary stem cells, with largely undefined functions. Here, we studied how vimentin deficiency affects mouse mammary gland development. We find that in adult vimentin knockout mice (Vim-/-) mammary ductal outgrowth is delayed. The adult Vim-/- glands display dilated ducts and reduced basal to luminal mouse mammary epithelial cell (MMEC) ratio indicative of altered progenitor cell activity...
September 25, 2017: Development
https://www.readbyqxmd.com/read/28940516/analysis-of-clonal-expansions-through-the-normal-and-premalignant-human-breast-epithelium-reveals-the-presence-of-luminal-stem-cells
#9
Biancastella Cereser, Marnix Jansen, Emily Austin, George Elia, Taneisha McFarlane, Carolien Hm van Deurzen, Anieta M Sieuwerts, Maria G Daidone, Paul J Tadrous, Nicholas A Wright, Louise Jones, Stuart Ac McDonald
It is widely accepted that the cell of origin of breast cancer is the adult mammary epithelial stem cell, however demonstrating the presence and location of tissue stem cells in the human breast has proved difficult. Furthermore, we do not know the clonal architecture of the normal and premalignant mammary epithelium or its cellular hierarchy. Here we use deficiency in the mitochondrial enzyme cytochrome c oxidase (CCO), typically caused by somatic mutations in the mitochondrial genome, as a means to perform lineage tracing in the human mammary epithelium...
September 22, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28938604/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#10
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938159/lunatic-fringe-and-p53-cooperatively-suppress-mesenchymal-stem-like-breast-cancer
#11
Wen-Cheng Chung, Shubing Zhang, Lavanya Challagundla, Yunyun Zhou, Keli Xu
Claudin-low breast cancer (CLBC) is a poor prognosis molecular subtype showing stemness and mesenchymal features. We previously discovered that deletion of a Notch signaling modulator, Lunatic Fringe (Lfng), in the mouse mammary gland induced a subset of tumors resembling CLBC. Here we report that deletion of one copy of p53 on this background not only accelerated mammary tumor development but also led to a complete penetrance of the mesenchymal stem-like phenotype. All mammary tumors examined in the Lfng/p53 compound mutant mice displayed a mesenchymal/spindloid pathology...
September 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28927044/isolation-and-characterization-of-adult-mammary-stem-cells-from-breast-cancer-adjacent-tissues
#12
Ai-Ping Shi, Zhi-Min Fan, Ke-Wei Ma, Yan-Fang Jiang, Lei Wang, Ke-Wei Zhang, Shi-Bo Fu, Ning Xu, Zhi-Ru Zhang
Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28919264/prolactin-alters-the-mammary-epithelial-hierarchy-increasing-progenitors-and-facilitating-ovarian-steroid-action
#13
Kathleen A O'Leary, Michael P Shea, Stephanie Salituro, Courtney E Blohm, Linda A Schuler
Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28904060/early-exposure-to-a-high-fat-high-sugar-diet-increases-the-mammary-stem-cell-compartment-and-mammary-tumor-risk-in-female-mice
#14
Isabel U Lambertz, Linjie Luo, Thomas R Berton, Scott L Schwartz, Stephen D Hursting, Claudio J Conti, Robin Fuchs-Young
Obesity and alterations in metabolic programming from early diet exposures can affect the propensity to disease in later life. Through dietary manipulation, developing mouse pups were exposed to a hyperinsulinemic, hyperglycemic milieu during three developmental phases: gestation, lactation, and postweaning. Analyses showed that a postweaning high fat/high sugar (HF/HS) diet had the main negative effect on adult body weight, glucose tolerance, and insulin resistance. However, dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis revealed that animals born to a mother fed a HF/HS gestation diet, nursed by a mother on a mildly diet-restricted, low fat/low sugar diet (DR) and weaned onto a HF/HS diet (HF/DR/HF) had the highest mammary tumor incidence, while HF/HF/DR had the lowest tumor incidence...
September 13, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28901484/molecular-iodine-impairs-chemoresistance-mechanisms-enhances-doxorubicin-retention-and-induces-downregulation-of-the-cd44-cd24-and-e-cadherin-vimentin-subpopulations-in-mcf-7-cells-resistant-to-low-doses-of-doxorubicin
#15
Alexander Bontempo, Brenda Ugalde-Villanueva, Evangelina Delgado-González, Ángel Luis Rodríguez, Carmen Aceves
One of the most dreaded clinical events for an oncology patient is resistance to treatment. Chemoresistance is a complex phenomenon based on alterations in apoptosis, the cell cycle and drug metabolism, and it correlates with the cancer stem cell phenotype and/or epithelial-mesenchymal transition. Molecular iodine (I2) exerts an antitumor effect on different types of iodine-capturing neoplasms by its oxidant/antioxidant properties and formation of iodolipids. In the present study, wild-type breast carcinoma cells (MCF-7/W) were treated chronically with 10 nM doxorubicin (DOX) to establish a low-dose DOX-resistant mammary cancer model (MCF-7/D)...
September 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28900173/fgfr-inhibitor-azd4547-impedes-the-stemness-of-mammary-epithelial-cells-in-the-premalignant-tissues-of-mmtv-erbb2-transgenic-mice
#16
Qingxia Zhao, Amanda B Parris, Erin W Howard, Ming Zhao, Zhikun Ma, Zhiying Guo, Ying Xing, Xiaohe Yang
The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases (RTKs) regulates signaling pathways involved in cell proliferation and differentiation. Currently, the anti-tumor properties of FGFR inhibitors are being tested in preclinical and clinical studies. Nevertheless, reports on FGFR inhibitor-mediated breast cancer prevention are sparse. In this study, we investigated the anti-cancer benefits of AZD4547, an FGFR1-3 inhibitor, in ErbB2-overexpressing breast cancer models. AZD4547 (1-5 µM) demonstrated potent anti-proliferative effects, inhibition of stemness, and suppression of FGFR/RTK signaling in ErbB2-overexpressing human breast cancer cells...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28891935/alteration-of-mammary-gland-development-and-gene-expression-by-in-utero-exposure-to-cadmium
#17
Daniela A Parodi, Morgan Greenfield, Claire Evans, Anna Chichura, Alexandra Alpaugh, James Williams, Kedra C Cyrus, Mary Beth Martin
Environmental exposure to estrogens and estrogen like contaminants during early development is thought to contribute to the risk of developing breast cancer primarily due to an early onset of puberty; however, exposure during key developing windows may also influence the risk of developing the disease. The goal of this study was to ask whether in utero exposure to the metalloestrogen cadmium alters mammary gland development due to acceleration of puberty onset or to an effect on early development of the mammary gland...
September 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28887477/neuropilin-1-is-upregulated-by-wnt-%C3%AE-catenin-signaling-and-is-important-for-mammary-stem-cells
#18
Wei Liu, Ting Wu, Xiaobing Dong, Yi Arial Zeng
Wnt/β-catenin signaling is instrumental for the development of mammary gland and the properties of mammary stem cells (MaSCs). The Wnt signaling downstream effectors that engage in regulating MaSCs have not been extensively studied. Here, we report that Neuropilin-1 (Nrp1) expression is induced by Wnt/β-catenin signaling in MaSCs, and its function is critical for the activity of MaSCs. Nrp1 is particularly expressed in MaSCs that are marked by the expression of Protein C Receptor (Procr). Knockdown of Nrp1 by shRNA diminishes MaSCs' in vitro colony formation and in vivo mammary gland reconstitution ability...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878809/are-online-prediction-tools-a-valid-alternative-to-genomic-profiling-in-the-context-of-systemic-treatment-of-er-positive-breast-cancer
#19
REVIEW
Umar Wazir, Kinan Mokbel, Amtul Carmichael, Kefah Mokbel
BACKGROUND: Clinicians use clinical and pathological parameters, such as tumour size, grade and nodal status, to make decisions on adjuvant treatments for breast cancer. However, therapeutic decisions based on these features tend to vary due to their subjectivity. Computational and mathematical algorithms were developed using clinical outcome data from breast cancer registries, such as Adjuvant! Online and NHS PREDICT. More recently, assessments of molecular profiles have been applied in the development of better prognostic tools...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28870991/receptor-protein-tyrosine-phosphatase-ptprb-negatively-regulates-fgf2-dependent-branching-morphogenesis
#20
Kelly J Soady, Giusy Tornillo, Howard Kendrick, Valerie Meniel, Daria Olijnyk-Dallis, Joanna S Morris, Torsten Stein, Barry A Gusterson, Clare M Isacke, Matthew J Smalley
PTPRB is a transmembrane protein tyrosine phosphatase known to regulate blood vessel remodelling and angiogenesis. Here we demonstrate that PTPRB negatively regulates branching morphogenesis in the mammary epithelium. We show that Ptprb is highly expressed in adult mammary stem cells and also, although at lower levels, in estrogen receptor positive luminal cells. During mammary development Ptprb expression is down-regulated during puberty, a period of extensive of ductal outgrowth and branching. In vivo shRNA knockdown of Ptprb in the cleared mammary fat pad transplant assay resulted in smaller epithelial outgrowths with an increased branching density and also increased branching in an in vitro organoid assay...
September 4, 2017: Development
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