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inflammatory breast cancer gene expression

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https://www.readbyqxmd.com/read/28333977/transition-into-inflammatory-cancer-associated-adipocytes-in-breast-cancer-microenvironment-requires-microrna-regulatory-mechanism
#1
Jiwoo Lee, Bok Sil Hong, Han Suk Ryu, Han-Byoel Lee, Minju Lee, In Ae Park, Jisun Kim, Wonshik Han, Dong-Young Noh, Hyeong-Gon Moon
The role of adipocytes in cancer microenvironment has gained focus during the recent years. However, the characteristics of the cancer-associated adipocytes (CAA) in human breast cancer tissues and the underlying regulatory mechanism are not clearly understood. We reviewed pathology specimens of breast cancer patients to understand the morphologic characteristics of CAA, and profiled the mRNA and miRNA expression of CAA by using indirect co-culture system in vitro. The CAAs in human breast cancers showed heterogeneous topographic relationship with breast cancer cells within the breast microenvironment...
2017: PloS One
https://www.readbyqxmd.com/read/28306507/structural-and-molecular-mechanisms-of-cytokine-mediated-endocrine-resistance-in-human-breast-cancer-cells
#2
Joshua D Stender, Jerome C Nwachukwu, Irida Kastrati, Yohan Kim, Tobias Strid, Maayan Yakir, Sathish Srinivasan, Jason Nowak, Tina Izard, Erumbi S Rangarajan, Kathryn E Carlson, John A Katzenellenbogen, Xin-Qiu Yao, Barry J Grant, Hon S Leong, Chin-Yo Lin, Jonna Frasor, Kendall W Nettles, Christopher K Glass
Human breast cancers that exhibit high proportions of immune cells and elevated levels of pro-inflammatory cytokines predict poor prognosis. Here, we demonstrate that treatment of human MCF-7 breast cancer cells with pro-inflammatory cytokines results in ERα-dependent activation of gene expression and proliferation, in the absence of ligand or presence of 4OH-tamoxifen (TOT). Cytokine activation of ERα and endocrine resistance is dependent on phosphorylation of ERα at S305 in the hinge domain. Phosphorylation of S305 by IKKβ establishes an ERα cistrome that substantially overlaps with the estradiol (E2)-dependent ERα cistrome...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28277986/bardoxolone-methyl-inhibits-migration-and-metabolism-in-mcf7-cells
#3
Alaa Refaat, Chathyan Pararasa, Muhammed Arif, James E P Brown, Amtul Carmichael, Sameh S Ali, Hiroaki Sakurai, Helen R Griffiths
Bardoxolone-methyl (BAR) is reported to have anti-inflammatory, anti-proliferative and anti-fibrotic effects. BAR activates Nrf2 and may ameliorate oxidative stress through induction of antioxidant genes. However, off-target effects, probably concentration and NFkB-dependent, have limited the clinical use of BAR. Nrf2 regulates expression of antioxidant and mitochondrial genes and has been proposed as a target for both obesity and breast cancer. Therefore, we explored whether BAR can alter migration and proliferation in the MCF7 cell line and whether metabolic function is affected by BAR...
February 2017: Free Radical Research
https://www.readbyqxmd.com/read/28256194/polymorphic-variations-associated-with-doxorubicin-induced-cardiotoxicity-in-breast-cancer-patients
#4
Valentina K Todorova, Issam Makhoul, Ishwori Dhakal, Jeanne Wei, Annjanette Stone, Weleetka Carter, Aaron Owen, V Suzanne Klimberg
Doxorubicin (DOX) is a commonly used antineoplastic agent for treatment of various malignancies, and its use is associated with unpredictable cardiotoxicity. Susceptibility to DOX cardiotoxicity is largely patient-dependent suggesting genetic predisposition. We have previously found that individual sensitivity to DOX-cardiotoxicity was associated with differential expression of genes implicated in inflammatory response and immune trafficking, which was consistent with the increasing number of reports highlighting the important role of HLA complex polymorphism in hypersensitivity to drug toxicity...
March 2, 2017: Oncology Research
https://www.readbyqxmd.com/read/28223235/interleukin-32-inflammation-and-cancer
#5
REVIEW
Jin Tae Hong, Dong Ju Son, Chong Kil Lee, Do-Young Yoon, Dong Hun Lee, Mi Hee Park
Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28212583/role-of-topk-in-lipopolysaccharide-induced-breast-cancer-cell-migration-and-invasion
#6
Min-Ah Seol, Jung-Hwan Park, Ji Heun Jeong, Jungmook Lyu, Seung Yun Han, Sang-Muk Oh
Inflammation has been known to be linked to invasion or metastasis of breast cancer, which has poor prognosis, although the regulatory mechanism remains to be undiscovered. Here we show that T-LAK cell-originated protein kinase (TOPK) mediates pro-inflammatory endotoxin lipopolysaccharide (LPS)-induced breast cancer cell migration and invasion. The mRNA or protein level of TOPK, toll- like receptor4 (TLR4), interleukin (IL)-6, vascular endothelial growth factor (VEGF) or matrix metalloproteinase9 (MMP9) genes related to TLR4 signaling or tumor progression was induced by LPS treatment in MCF7 breast cancer cells, but the induction was abolished by stable knocking down of TOPK in MCF7 cells...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28207963/nardilysin-promotes-hepatocellular-carcinoma-through-activation-of-signal-transducer-and-activator-of-transcription-3
#7
Yosuke Kasai, Kan Toriguchi, Etsuro Hatano, Kiyoto Nishi, Mikiko Ohno, Tomoaki Yoh, Keita Fukuyama, Takahiro Nishio, Masayuki Okuno, Keiko Iwaisako, Satoru Seo, Kojiro Taura, Masato Kurokawa, Makoto Kunichika, Shinji Uemoto, Eiichiro Nishi
Nardilysin (NRDC) is a metalloendopeptidase of the M16 family. We previously showed that NRDC activates inflammatory cytokine signaling, including interleukin-6-signal transducer and activator of transcription 3 (STAT3) signaling. NRDC has been implicated in the promotion of breast, gastric, and esophageal cancer, as well as the development of liver fibrosis. In this study, we investigated the role of NRDC in the promotion of hepatocellular carcinoma (HCC), both clinically and experimentally. We found that NRDC expression was up-regulated 3-fold in HCC tissue compared to the adjacent non-tumor liver tissue, which was confirmed by immunohistochemistry and western blotting...
February 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28117419/time-of-day-dictates-transcriptional-inflammatory-responses-to-cytotoxic-chemotherapy
#8
Jeremy C Borniger, William H Walker Ii, Monica M Gaudier-Diaz, Curtis J Stegman, Ning Zhang, Jennifer L Hollyfield, Randy J Nelson, A Courtney DeVries
Many cytotoxic chemotherapeutics elicit a proinflammatory response which is often associated with chemotherapy-induced behavioral alterations. The immune system is under circadian influence; time-of-day may alter inflammatory responses to chemotherapeutics. We tested this hypothesis by administering cyclophosphamide and doxorubicin (Cyclo/Dox), a common treatment for breast cancer, to female BALB/c mice near the beginning of the light or dark phase. Mice were injected intravenously with Cyclo/Dox or the vehicle two hours after lights on (zeitgeber time (ZT2), or two hours after lights off (ZT14)...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108626/a-new-role-for-er%C3%AE-silencing-via-dna-methylation-of-basal-stem-cell-and-emt-genes
#9
Eric A Ariazi, John C Taylor, Michael A Black, Emmanuelle Nicolas, Michael J Slifker, Diana J Azzam, Jeff Boyd
Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α-positive (ERα(+)) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα(+) status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα(+) cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression...
February 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28106823/integrated-microrna-mrna-profiling-identifies-oncostatin-m-as-a-marker-of-mesenchymal-like-er-negative-her2-negative-breast-cancer
#10
Giulia Bottai, Lixia Diao, Keith A Baggerly, Laura Paladini, Balázs Győrffy, Carlotta Raschioni, Lajos Pusztai, George A Calin, Libero Santarpia
MicroRNAs (miRNAs) simultaneously modulate different oncogenic networks, establishing a dynamic system of gene expression and pathway regulation. In this study, we analyzed global miRNA and messenger RNA (mRNA) expression profiles of 17 cell lines representing different molecular breast cancer subtypes. Spearman's rank correlation test was used to evaluate the correlation between miRNA and mRNA expression. Hierarchical clustering and pathway analysis were also performed. Publicly available gene expression profiles (n = 699) and tumor tissues (n = 80) were analyzed to assess the relevance of key miRNA-regulated pathways in human breast cancer...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28099924/microrna-140-mediates-rb-tumor-suppressor-function-to-control-stem-cell-like-activity-through-interleukin-6
#11
Akiyo Yoshida, Shunsuke Kitajima, Fengkai Li, Chaoyang Cheng, Yujiro Takegami, Susumu Kohno, Yuan Song Wan, Naoyuki Hayashi, Hayato Muranaka, Yuuki Nishimoto, Naoko Nagatani, Takumi Nishiuchi, Tran C Thai, Sawako Suzuki, Shinji Nakao, Tomoaki Tanaka, Osamu Hirose, David A Barbie, Chiaki Takahashi
We established an in vitro cell culture system to determine novel activities of the retinoblastoma (Rb) protein during tumor progression. Rb depletion in p53-null mouse-derived soft tissue sarcoma cells induced a spherogenic phenotype. Cells retrieved from Rb-depleted spheres exhibited slower proliferation and less efficient BrdU incorporation, however, much higher spherogenic activity and aggressive behavior. We discovered six miRNAs, including mmu-miR-18a, -25, -29b, -140, -337, and -1839, whose expression levels correlated tightly with the Rb status and spherogenic activity...
January 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28093282/il-1%C3%AE-induces-up-regulation-of-birc3-a-gene-involved-in-chemoresistance-to-doxorubicin-in-breast-cancer-cells
#12
Mónica Mendoza-Rodríguez, Haruki Arévalo Romero, Ezequiel M Fuentes-Pananá, Jorge-Tonatiuh Ayala-Sumuano, Isaura Meza
Epithelial to mesenchymal transition (EMT) of tumor cells facilitates their progress to metastasis. In the tumor microenvironment the inflammatory cytokine 1β (IL-1β) has been associated with tumor development and invasiveness. IL-1β-induced EMT triggers the expression of markers associated with malignancy. We have recently reported that an IL-1β-highly responsive clone (6D cells) from non-invasive MCF-7 breast cancer cells activates PI3K/Rac and IL-1RI/β-catenin pathways that up-regulate the transcription of genes involved in an EMT-like process...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28075192/loss-of-monocyte-chemoattractant-protein-1-expression-delays-mammary-tumorigenesis-and-reduces-localized-inflammation-in-the-c3-1-sv40tag-triple-negative-breast-cancer-model
#13
Taryn L Cranford, Kandy T Velázquez, Reilly T Enos, Jackie E Bader, Meredith S Carson, Ioulia Chatzistamou, Mitzi Nagarkatti, E Angela Murphy
Monocyte chemoattractant protein 1 (MCP-1) has been implicated as a major modulator in the progression of mammary tumorigenesis, largely due to its ability to recruit macrophages to the tumor microenvironment. Macrophages are key mediators in the connection between inflammation and cancer progression and have been shown to play an important role in tumorigenesis. Thus, MCP-1 may be a potential therapeutic target in inflammatory and difficult-to-treat cancers such as triple negative breast cancer (TNBC). We examined the effect of MCP-1 depletion on mammary tumorigenesis in a model of TNBC...
February 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28052038/competing-endogenous-rna-network-analysis-identifies-critical-genes-among-the-different-breast-cancer-subtypes
#14
Juan Chen, Juan Xu, Yongsheng Li, Jinwen Zhang, Hong Chen, Jianping Lu, Zishan Wang, Xueying Zhao, Kang Xu, Yixue Li, Xia Li, Yan Zhang
Although competing endogenous RNAs (ceRNAs) have been implicated in many solid tumors, their roles in breast cancer subtypes are not well understood. We therefore generated a ceRNA network for each subtype based on the significance of both, positive co-expression and the shared miRNAs, in the corresponding subtype miRNA dys-regulatory network, which was constructed based on negative regulations between differentially expressed miRNAs and targets. All four subtype ceRNA networks exhibited scale-free architecture and showed that the common ceRNAs were at the core of the networks...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28051153/the-metastasis-suppressor-rarres3-as-an-endogenous-inhibitor-of-the-immunoproteasome-expression-in-breast-cancer-cells
#15
Alison M Anderson, Murugan Kalimutho, Sarah Harten, Devathri M Nanayakkara, Kum Kum Khanna, Mark A Ragan
In breast cancer metastasis, the dynamic continuum involving pro- and anti-inflammatory regulators can become compromised. Over 600 genes have been implicated in metastasis to bone, lung or brain but how these genes might contribute to perturbation of immune function is poorly understood. To gain insight, we adopted a gene co-expression network approach that draws on the functional parallels between naturally occurring bone marrow-derived mesenchymal stem cells (BM-MSCs) and cancer stem cells (CSCs). Our network analyses indicate a key role for metastasis suppressor RARRES3, including potential to regulate the immunoproteasome (IP), a specialized proteasome induced under inflammatory conditions...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28003476/efficient-dna-binding-of-nf-%C3%AE%C2%BAb-requires-the-chaperone-like-function-of-npm1
#16
Jianhuang Lin, Mitsuyasu Kato, Kyosuke Nagata, Mitsuru Okuwaki
NPM1/nucleophosmin is frequently overexpressed in various tumors, although the oncogenic role of NPM1 remains unclear. Here we revealed the link between NPM1 and nuclear factor-κB (NF-κB), a master regulator of inflammation. We found that NPM1 knockdown decreased NF-κB-mediated transcription of selected target genes by decreasing the recruitment of NF-κB p65 to the gene promoters. NPM1 is directly associated with the DNA binding domain of p65 to enhance its DNA binding activity without being a part of the DNA-NF-κB complex...
December 20, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27940607/synergistic-drug-combinations-from-electronic-health-records-and-gene-expression
#17
Yen S Low, Aaron C Daugherty, Elizabeth A Schroeder, William Chen, Tina Seto, Susan Weber, Michael Lim, Trevor Hastie, Maya Mathur, Manisha Desai, Carl Farrington, Andrew A Radin, Marina Sirota, Pragati Kenkare, Caroline A Thompson, Peter P Yu, Scarlett L Gomez, George W Sledge, Allison W Kurian, Nigam H Shah
OBJECTIVE: Using electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding. METHOD: We applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients...
December 9, 2016: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/27881676/cytoplasmic-localization-of-proline-glutamic-acid-leucine-rich-protein-1-pelp1-induces-breast-epithelial-cell-migration-through-up-regulation-of-inhibitor-of-%C3%AE%C2%BAb-kinase-%C3%AF%C2%B5-and-inflammatory-cross-talk-with-macrophages
#18
Brian J Girard, Todd P Knutson, Bethanie Kuker, Laura McDowell, Kathryn L Schwertfeger, Julie H Ostrander
Cytoplasmic localization of proline, glutamic acid, leucine-rich protein 1 (PELP1) is observed in ∼40% of women with invasive breast cancer. In mouse models, PELP1 overexpression in the mammary gland leads to premalignant lesions and eventually mammary tumors. In preliminary clinical studies, cytoplasmic localization of PELP1 was seen in 36% of women at high risk of developing breast cancer. Here, we investigated whether cytoplasmic PELP1 signaling promotes breast cancer initiation in models of immortalized human mammary epithelial cells (HMECs)...
January 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27865894/activation-of-peroxisome-proliferator-activated-receptor-gamma-in-mammary-epithelial-cells-upregulates-the-expression-of-tumor-suppressor-cyld-to-mediate-growth-inhibition-and-anti-inflammatory-effects
#19
Athanasios Pseftogas, Christos Gonidas, George Mosialos
Several studies have implicated the downregulation of the tumor suppressor Cyld expression in breast cancer development. However, the mechanisms that regulate Cyld expression in mammary epithelial cells are largely unknown. In order to investigate them, a bioinformatic analysis of the promoter region of Cyld was performed and identified putative nuclear hormone receptor response elements that included peroxisome proliferator-activated receptor gamma (PPAR-γ)-responsive elements. In the present study, we showed that upon activation of the nuclear hormone receptor PPAR-γ by the agonist troglitazone (TZD), there was a significant increase in Cyld mRNA in human mammary epithelial cell lines...
January 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27852980/aging-is-associated-with-an-expansion-of-cd49f-hi-mammary-stem-cells-that-show-a-decline-in-function-and-increased-transformation-potential
#20
Qiaoxiang Dong, Hui Gao, Yuanshuo Shi, Fuchuang Zhang, Xiang Gu, Anqi Wu, Danhan Wang, Yuanhong Chen, Abhik Bandyopadhyay, I-Tien Yeh, Benjamin J Daniel, Yidong Chen, Yi Zou, Vivienne L Rebel, Christi A Walter, Jianxin Lu, Changjiang Huang, Lu-Zhe Sun
Breast cancer incidence increases during aging, yet the mechanism of age-associated mammary tumorigenesis is unclear. Mammary stem cells are believed to play an important role in breast tumorigenesis, but how their function changes with age is unknown. We compared mammary epithelial cells isolated from young and old mammary glands of different cohorts of C57BL6/J and BALB/c mice, and our findings revealed that old mammary glands were characterized by increased basal cell pool comprised of mostly CD49f(hi) cells, altered luminal-to-basal cell ratio, and irregular ductal morphology...
November 15, 2016: Aging
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