scholarly journals Alterations of EGFR, p53 and PTEN that mimic changes found in basal-like breast cancer promote transformation of human mammary epithelial cells

2013 ◽  
Vol 14 (3) ◽  
pp. 246-253 ◽  
Author(s):  
Maira M. Pires ◽  
Benjamin D. Hopkins ◽  
Lao H. Saal ◽  
Ramon E. Parsons
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Human Mammary Epithelial Cells ◽  
Human Mammary Epithelial ◽  
Basal Like Breast Cancer

scholarly journals YB-1 Transforms Human Mammary Epithelial Cells Through Chromatin Remodeling Leading to the Development of Basal-Like Breast Cancer

Stem Cells ◽  
2014 ◽  
Vol 32 (6) ◽  
pp. 1437-1450 ◽  
Author(s):  
Alastair H. Davies ◽  
Kristen M. Reipas ◽  
Mary Rose Pambid ◽  
Rachel Berns ◽  
Anna L. Stratford ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Chromatin Remodeling ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Human Mammary Epithelial Cells ◽  
Human Mammary Epithelial ◽  
Basal Like Breast Cancer

scholarly journals Attenuation of TGF-β signaling suppresses premature senescence in a p21-dependent manner and promotes oncogenic Ras-mediated metastatic transformation in human mammary epithelial cells

2012 ◽  
Vol 23 (8) ◽  
pp. 1569-1581 ◽  
Author(s):  
Shu Lin ◽  
Junhua Yang ◽  
Abdel G. Elkahloun ◽  
Abhik Bandyopadhyay ◽  
Long Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Dependent Manner ◽  
Human Mammary Epithelial Cells ◽  
Major Player ◽  
Human Mammary Epithelial ◽  
Basal Like Breast Cancer

The molecular mechanisms that drive triple-negative, basal-like breast cancer progression are elusive. Few molecular targets have been identified for the prevention or treatment of this disease. Here we developed a series of isogenic basal-like human mammary epithelial cells (HMECs) with altered transforming growth factor-β (TGF-β) sensitivity and different malignancy, resembling a full spectrum of basal-like breast carcinogenesis, and determined the molecular mechanisms that contribute to oncogene-induced transformation of basal-like HMECs when TGF-β signaling is attenuated. We found that expression of a dominant-negative type II receptor (DNRII) of TGF-β abrogated autocrine TGF-β signaling in telomerase-immortalized HMECs and suppressed H-Ras-V12–induced senescence-like growth arrest (SLGA). Furthermore, coexpression of DNRII and H-Ras-V12 rendered HMECs highly tumorigenic and metastatic in vivo in comparison with H-Ras-V12–transformed HMECs that spontaneously escaped H-Ras-V12–induced SLGA. Microarray analysis revealed that p21 was the major player mediating Ras-induced SLGA, and attenuated or loss of p21 expression contributed to the escape from SLGA when autocrine TGF-β signaling was blocked in HMECs. Furthermore, knockdown of p21 also suppressed H-Ras-V12–induced SLGA. Our results identify that autocrine TGF-β signaling is an integral part of the cellular anti-transformation network by suppressing the expression of a host of genes, including p21-regulated genes, that mediate oncogene-induced transformation in basal-like breast cancer.

scholarly journals c-Myc Transforms Human Mammary Epithelial Cells through Repression of the Wnt Inhibitors DKK1 and SFRP1

2007 ◽  
Vol 27 (14) ◽  
pp. 5135-5146 ◽  
Author(s):  
Victoria H. Cowling ◽  
Celina M. D'Cruz ◽  
Lewis A. Chodosh ◽  
Michael D. Cole
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Target Genes ◽  
Mammary Epithelial Cells ◽  
Tumor Formation ◽  
Mammary Epithelial ◽  
Breast Cancer Cell Lines ◽  
Human Mammary Epithelial Cells ◽  
Human Mammary Epithelial ◽  
Wnt Inhibitors

ABSTRACT c-myc is frequently amplified in breast cancer; however, the mechanism of myc-induced mammary epithelial cell transformation has not been defined. We show that c-Myc induces a profound morphological transformation in human mammary epithelial cells and anchorage-independent growth. c-Myc suppresses the Wnt inhibitors DKK1 and SFRP1, and derepression of DKK1 or SFRP1 reduces Myc-dependent transforming activity. Myc-dependent repression of DKK1 and SFRP1 is accompanied by Wnt target gene activation and endogenous T-cell factor activity. Myc-induced mouse mammary tumors have repressed SFRP1 and increased expression of Wnt target genes. DKK1 and SFRP1 inhibit the transformed phenotype of breast cancer cell lines, and DKK1 inhibits tumor formation. We propose a positive feedback loop for activation of the c-myc and Wnt pathways in breast cancer.

scholarly journals Microtubule Hyperacetylation Enhances KL1-Dependent Micronucleation under a Tau Deficiency in Mammary Epithelial Cells

2018 ◽  
Vol 19 (9) ◽  
pp. 2488 ◽  
Author(s):  
Haruka Sudo
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Prognostic Indicator ◽  
Mammary Epithelial ◽  
Breast Carcinogenesis ◽  
Human Mammary Epithelial Cells ◽  
Human Mammary Epithelial ◽  
Rat Fibroblasts ◽  
Spindle Microtubules

Enhanced microtubule acetylation has been identified as a negative prognostic indicator in breast cancer. We reported previously that primary cultured human mammary epithelial cells manifest breast cancer-related aneuploidization via the activation of severing protein katanin-like (KL)1 when tau is deficient. To address in this current study whether microtubule hyperacetylation is involved in breast carcinogenesis through mitosis, the effects of tubacin on human mammary epithelial cells were tested using immunofluorescence techniques. Tau-knockdown cells showed enhancement of KL1-dependent events, chromosome-bridging and micronucleation in response to tubacin. These enhancements were suppressed by further expression of an acetylation-deficient tubulin mutant. Consistently, using a rat fibroblast-based microtubule sensitivity test, it was confirmed that KL1 also shows enhanced activity in response to microtubule hyperacetylation as well as katanin. It was further observed in rat fibroblasts that exogenously expressed KL1 results in more micronucleation under microtubule hyperacetylation conditions. These data suggest that microtubule acetylation upregulates KL1 and induces more aneuploidy if tau is deficient. It is thus plausible that microtubule hyperacetylation promotes tumor progression by enhancing microtubule sensitivity to KL1, thereby disrupting spindle microtubules and this process could be reversed by the microtubule-binding and microtubule protective octapeptide NAPVSIPQ (NAP) which recruits tau to the microtubules.

scholarly journals Distinct oncogenes drive distinct genome and epigenome alterations in human mammary epithelial cells

2018 ◽  
Author(s):  
Claire Fonti ◽  
Anne Saumet ◽  
Amanda Abi-Khalil ◽  
Béatrice Orsetti ◽  
William Jacot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Cell Lineages ◽  
Human Mammary Epithelial Cells ◽  
Early Activation ◽  
Oncogenic Pathways ◽  
Human Mammary Epithelial

AbstractGene expression differences, combined with distinct patterns of genomic rearrangements and epigenetic modifications, have laid the bases of molecular classification of breast cancer. Different molecular subtypes are thought to originate from different cell lineages in the mammary gland, but the early activation of an oncogene could also play a role. It is, however, difficult to discriminate the respective inputs of oncogene activation or cell type of origin in the natural history of the tumor. In this work, we have designed an experimental strategy aiming at determining whether activation of distinct oncogenic pathways in human mammary epithelial cells (HMEC) could lead to different patterns of genetic and epigenetic changes. We show that initial activation of CCNE1, WNT1 and RASv12, which activate distinct oncogenic pathways, in shp53 immortalized HMECs results in different and reproducible profiles of mRNA and miRNA expression, copy number alterations (CNA) and DNA methylation modifications. Noticeably, HMECs transformed by RAS bore very specific profiles of CNAs and DNA methylation, clearly distinct from those shown by CCNE1 and WNT1 transformed HMECs.Genes impacted by CNAs and CpG methylation in the RAS and the CCNE1/WNT1 clusters showed clear differences, illustrating the activation of distinct pathways. Our data show that early activation of distinct oncogenic pathways leads to active adaptive events resulting in specific sets of CNAs and DNA methylation changes. We, thus, propose that activation of different oncogenes could have a role in reshaping the genetic landscape of breast cancer subtypes.Author summaryGenetic and epigenetic changes are at the center of cancer development. Breast cancer molecular subtypes are defined on differences in genetic and epigenetic profiles and it is generally assumed these subtypes originate from different cell lineages in the mammary gland. We propose that founding oncogenic mutations could also have an impact. To address this question, we designed an experimental model, based on the ectopic expression of different oncogenes in human mammary epithelial cells (HMEC), and monitored genetic and DNA methylation changes occurring at different stages of cell transformation. We show that transformation of HMEC by distinct oncogenes resulted in clearly different and reproducible patterns of genetic and DNA methylation changes. Genes whose expression was modified by either CNAs or CpG methylation were consistent with the dominant pathways activated and reflected the phenotypes in the respective models. We propose that DNA methylation and CNA changes correspond to adaptive responses to the activation of the oncogenic pathways. Our data strongly suggest that early activation of distinct oncogenic insults will not only impinge on the phenotypic characteristics of the resulting tumors, but also have a strong impact on their genomic and epigenetic landscapes.

scholarly journals Distinct Oncogenic Transcriptomes in Human Mammary Epithelial Cells Infected With Cytomegalovirus

2021 ◽  
Vol 12 ◽  
Author(s):  
Sandy Haidar Ahmad ◽  
Sébastien Pasquereau ◽  
Ranim El Baba ◽  
Zeina Nehme ◽  
Clara Lewandowski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Low Risk ◽  
Human Mammary Epithelial Cells ◽  
Mammosphere Formation ◽  
Human Mammary Epithelial

Human cytomegalovirus is being recognized as a potential oncovirus beside its oncomodulation role. We previously isolated two clinical isolates, HCMV-DB (KT959235) and HCMV-BL (MW980585), which in primary human mammary epithelial cells promoted oncogenic molecular pathways, established anchorage-independent growth in vitro, and produced tumorigenicity in mice models, therefore named high-risk oncogenic strains. In contrast, other clinical HCMV strains such as HCMV-FS, KM, and SC did not trigger such traits, therefore named low-risk oncogenic strains. In this study, we compared high-risk oncogenic HCMV-DB and BL strains (high-risk) with low-risk oncogenic strains HCMV-FS, KM, and SC (low-risk) additionally to the prototypic HCMV-TB40/E, knowing that all strains infect HMECs in vitro. Numerous pro-oncogenic features including enhanced expression of oncogenes, cell survival, proliferation, and epithelial-mesenchymal transition genes were observed with HCMV-BL. In vitro, mammosphere formation was observed only in high-risk strains. HCMV-TB40/E showed an intermediate transcriptome landscape with limited mammosphere formation. Since we observed that Ki67 gene expression allows us to discriminate between high and low-risk HCMV strains in vitro, we further tested its expression in vivo. Among HCMV-positive breast cancer biopsies, we only detected high expression of the Ki67 gene in basal tumors which may correspond to the presence of high-risk HCMV strains within tumors. Altogether, the transcriptome of HMECs infected with HCMV clinical isolates displays an “oncogenic gradient” where high-risk strains specifically induce a prooncogenic environment which might participate in breast cancer development.

scholarly journals Bisphenol S and Bisphenol A disrupt morphogenesis of MCF-12A human mammary epithelial cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ella Atlas ◽  
Valeria Dimitrova
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Bisphenol A ◽  
Mammary Epithelial Cells ◽  
Environmental Pollutants ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Bisphenol S ◽  
Human Mammary Epithelial Cells ◽  
Human Mammary Epithelial

Abstract Breast cancer is one of the most common cancers diagnosed in women worldwide. Genetic predisposition, such as breast cancer 1 (BRCA1) mutations, account for a minor percentage of the total breast cancer incidences. And thus, many life style factors have also been linked to the disease such as smoking, alcohol consumption and obesity. Emerging studies show that environmental pollutants may also play a role. Bisphenol-A (BPA) has been suspected to contribute to breast cancer development, and has been shown to affect mammary gland development amongst other effects. This prompted its replacement with other bisphenol analogs such as, bisphenol-S (BPS). In this study we used the human mammary epithelial cells, MCF-12A, grown in extracellular matrix to investigate the ability of BPA and BPS to disrupt mammary epithelial cells organization. We show that both BPA and BPS were equipotent in disrupting the organization of the acinar structures, despite BPS being less oestrogenic by other assays. Further, treatment with both compounds enabled the cells to invade the lumen of the structures. This study shows that BPS and BPA are environmental pollutants that may affect mammary development and may contribute to the development of breast cancer.

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