Identification of H-Ras-Specific Motif for the Activation of Invasive Signaling Program in Human Breast Epithelial Cells

Hao, Yaxing; Hwang, Jiyoung; Son, Hwajin; Park, Hae In; Oh, Eok Soo; Kim, Hyun-Hwi; Kim, Do Kyun; Choi, Wahn Soo; Lee, Bong Jin; Kim, Hyeong Reh Choi; Moon, Aree

doi:10.1593/neo.101088

Cited by 33 publications

(35 citation statements)

References 40 publications

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“…Ras genes are involved in a wide variety of human tumor types and there is a known positive correlation between HRAS activation and breast cancer (33). In addition, previous studies (34,35) have shown that HRAS can induce invasion and migration of the breast cancer cell line, MCF10A. From the present study, HRAS may serve a significant role in the pathogenesis of TNBC and, given its functional significance in various types of cancer, it may also be a potential therapeutic target in the treatment of TNBC.…”

Section: Discussionsupporting

confidence: 70%

Integrated analysis of differentially expressed genes and pathways in triple-negative breast cancer

Peng

Xia

et al. 2017

Molecular Medicine Reports

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Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by an aggressive phenotype and reduced survival. The aim of the present study was to investigate the molecular mechanisms involved in the carcinogenesis of TNBC and to identify novel target molecules for therapy. The differentially expressed genes (DEGs) in TNBC and normal adjacent tissue were assessed by analyzing the GSE41970 microarray data using Qlucore Omics Explorer, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes. Pathway enrichment analyses for DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery online resource. A protein-protein interaction (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes, and subnetworks were analyzed by ClusterONE. The PPI network and subnetworks were visualized using Cytoscape software. A total of 121 DEGs were obtained, of which 101 were upregulated and 20 were downregulated. The upregulated DEGs were significantly enriched in 14 pathways and 83 GO biological processes, while the downregulated DEGs were significantly enriched in 18 GO biological processes. The PPI network with 118 nodes and 1,264 edges was constructed and three subnetworks were extracted from the entire network. The significant hub DEGs with high degrees were identified, including TP53, glyceraldehyde-3-phosphate dehydrogenase, cyclin D1, HRAS and proliferating cell nuclear antigen, which were predominantly enriched in the cell cycle pathway and pathways in cancer. A number of critical genes and pathways were revealed to be associated with TNBC. The present study may provide an improved understanding of the pathogenesis of TNBC and contribute to the development of therapeutic targets for TNBC.

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Section: Discussionsupporting

confidence: 70%

Integrated analysis of differentially expressed genes and pathways in triple-negative breast cancer

Peng

Xia

et al. 2017

Molecular Medicine Reports

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“…Although the cultured CTCs obtained from patient AMC-15-06 did not have any of the COSMIC database identified mutations also identified in the primary tumor tissue, a mutation of HRAS was detected in CTCs of this patient that has previously been reported to be associated with breast cancer recurrence and metastasis (27,28). …”

Section: Discussionmentioning

confidence: 78%

Cancer gene panel analysis of cultured circulating tumor cells and primary tumor tissue from patients with breast cancer

Hwang¹,

Uh²,

Lee³

et al. 2017

Oncology Letters

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Although numerous effective therapies have improved the survival rate of patients with breast cancer, a number of patients present with tumor recurrence and metastasis. A liquid biopsy of circulating tumor cells (CTC) is a non-invasive method to obtain tumor cells and may be used as substitute for a tumor tissue biopsy. The present study focuses on determining whether CTC culture is an optimal method of obtaining sufficient amounts of CTCs for molecular analysis. The current study demonstrates a method of isolating and culturing CTCs from patients with breast cancer and the construction of a molecular profile of cultured cells using the Ion AmpliSeq Cancer Gene Panel V2. Gene mutations that were observed in cultured CTCs were compared with those observed in primary tumor tissues. CTCs were isolated and cultured from the blood of six patients with breast cancer. Mutations from the Catalogue Of Somatic Mutation In Cancer (COSMIC) were detected in Platelet-Derived Growth Factor Receptor Alpha, MET (also known as Hepatocyte Growth Factor Receptor), Phosphatase and Tensin Homolog, Harvey Rat Sarcoma Viral Oncogene Homolog, SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin Subfamily B Member 1, Cyclin Dependent Kinase Inhibitor 2A and MutL Homolog 1 genes in 5/6 samples. A comparison between mutations detected in cultured CTCs and mutations detected in primary tumor tissues demonstrated that a large number of mutations that were identified in CTCs were also detected in primary tumor tissues. The results from the current study describe a novel cell culture approach that may be used to obtain an optimal number of CTCs for molecular analysis. This novel approach is able to be used as a tool for liquid biopsy during breast cancer treatment.

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“…71 A high level of MMP-9 expression was detected at sites of inflammation, thus promoting migration of inflammatory cells across the basement membrane. 72 Interestingly, we have previously shown that MMP-2, rather than MMP-9, is responsible for the invasive phenotype induced by H-Ras and G a12/13 in MCF10A human breast epithelial cells, [73][74][75][76] suggesting differential regulation of MMP-2 and MMP-9, depending on the type of stimuli.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

et al. 2013

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A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional significance in breast cell invasion. The present study aimed to elucidate the molecular link between S1P and CRP during the invasive process of breast epithelial cells. This is the first report showing that transcription of CRP was markedly activated by S1P in breast cells. Our data suggest that not only S1P treatment but also the endogenously produced S1P may upregulate CRP in breast carcinoma cells. Transcription factors CCAAT/enhancer-binding protein beta and c-fos were required for S1P-induced CRP expression. Coupling of S1P3 to heterotrimeric Gαq triggered the expression of CRP, utilizing signaling pathways involving reactive oxygen species (ROS), Ca(2+) and extracellular signal-related kinases (ERKs). S1P-induced CRP expression was crucial for the transcriptional activation of matrix metalloproteinase-9 through ERKs, ROS and c-fos, leading to breast cell invasion. Using a xenograft mice tumor model, we demonstrated that S1P induced CRP expression both in vitro and in vivo. Taken together, our findings have revealed a molecular basis for S1P-induced transcriptional activation of CRP and its functional significance in the acquisition of the invasive phenotype of human breast epithelial cells under inflammatory conditions. Our findings may provide useful information on the identification of useful therapeutic targets for inflammatory breast cancer.

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Identification of H-Ras-Specific Motif for the Activation of Invasive Signaling Program in Human Breast Epithelial Cells

Cited by 33 publications

References 40 publications

Integrated analysis of differentially expressed genes and pathways in triple-negative breast cancer

Integrated analysis of differentially expressed genes and pathways in triple-negative breast cancer

Cancer gene panel analysis of cultured circulating tumor cells and primary tumor tissue from patients with breast cancer

Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

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