scholarly journals Chemically Induced Hypoxia Enhances miRNA Functions in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2008 ◽  
Author(s):  
Emma Gervin ◽  
Bonita Shin ◽  
Reid Opperman ◽  
Mackenzie Cullen ◽  
Riley Feser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Metastatic Breast ◽  
Breast Tumors ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells ◽  
Cox 2

In aggressively growing tumors, hypoxia induces HIF-1α expression promoting angiogenesis. Previously, we have shown that overexpression of oncogenic microRNAs (miRNAs, miRs) miR526b/miR655 in poorly metastatic breast cancer cell lines promotes aggressive cancer phenotypes in vitro and in vivo. Additionally, miR526b/miR655 expression is significantly higher in human breast tumors, and high miR526b/miR655 expression is associated with poor prognosis. However, the roles of miR526b/miR655 in hypoxia are unknown. To test the relationship between miR526b/miR655 and hypoxia, we used various in vitro, in silico, and in situ assays. In normoxia, miRNA-high aggressive breast cancer cell lines show higher HIF-1α expression than miRNA-low poorly metastatic breast cancer cell lines. To test direct involvement of miR526b/miR655 in hypoxia, we analyzed miRNA-high cell lines (MCF7-miR526b, MCF7-miR655, MCF7-COX2, and SKBR3-miR526b) compared to controls (MCF7 and SKBR3). CoCl2-induced hypoxia in breast cancer further promotes HIF-1α mRNA and protein expression while reducing VHL expression (a negative HIF-1α regulator), especially in miRNA-high cell lines. Hypoxia enhances oxidative stress, epithelial to mesenchymal transition, cell migration, and vascular mimicry more prominently in MCF7-miR526b/MCF7-miR655 cell lines compared to MCF7 cells. Hypoxia promotes inflammatory and angiogenesis marker (COX-2, EP4, NFκB1, VEGFA) expression in all miRNA-high cells. Hypoxia upregulates miR526b/miR655 expression in MCF7 cells, thus observed enhancement of hypoxia-induced functions in MCF7 could be attributed to miR526b/miR655 upregulation. In silico bioinformatics analysis shows miR526b/miR655 regulate PTEN (a negative regulator of HIF-1α) and NFκB1 (positive regulator of COX-2 and EP4) expression by downregulation of transcription factors NR2C2, SALL4, and ZNF207. Hypoxia-enhanced functions in miRNA-high cells are inhibited by COX-2 inhibitor (Celecoxib), EP4 antagonist (ONO-AE3-208), and irreversible PI3K/Akt inhibitor (Wortmannin). This establishes that hypoxia enhances miRNA functions following the COX-2/EP4/PI3K/Akt pathways and this pathway can serve as a therapeutic target to abrogate hypoxia and miRNA induced functions in breast cancer. In situ, HIF-1α expression is significantly higher in human breast tumors (n = 96) compared to non-cancerous control tissues (n = 20) and is positively correlated with miR526b/miR655 expression. In stratified tumor samples, HIF-1α expression was significantly higher in ER-positive, PR-positive, and HER2-negative breast tumors. Data extracted from the TCGA database also show a strong correlation between HIF-1α and miRNA-cluster expression in breast tumors. This study, for the first time, establishes the dynamic roles of miR526b/miR655 in hypoxia.

scholarly journals Overexpression of COX-2 in Celecoxib-Resistant Breast Cancer Cell Lines

2010 ◽  
Vol 163 (2) ◽  
pp. 235-243 ◽  
Author(s):  
Balraj Singh ◽  
LaTashia R. Irving ◽  
Karen Tai ◽  
Anthony Lucci
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cox 2 ◽  
Resistant Breast Cancer Cell

scholarly journals Deciphering the Correlation between Breast Tumor Samples and Cell Lines by Integrating Copy Number Changes and Gene Expression Profiles

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Yi Sun ◽  
Qi Liu
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Breast Tumors ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Tumor Group

Breast cancer is one of the most common cancers with high incident rate and high mortality rate worldwide. Although different breast cancer cell lines were widely used in laboratory investigations, accumulated evidences have indicated that genomic differences exist between cancer cell lines and tissue samples in the past decades. The abundant molecular profiles of cancer cell lines and tumor samples deposited in the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas now allow a systematical comparison of the breast cancer cell lines with breast tumors. We depicted the genomic characteristics of breast primary tumors based on the copy number variation and gene expression profiles and the breast cancer cell lines were compared to different subgroups of breast tumors. We identified that some of the breast cancer cell lines show high correlation with the tumor group that agrees with previous knowledge, while a big part of them do not, including the most used MCF7, MDA-MB-231, and T-47D. We presented a computational framework to identify cell lines that mostly resemble a certain tumor group for the breast tumor study. Our investigation presents a useful guide to bridge the gap between cell lines and tumors and helps to select the most suitable cell line models for personalized cancer studies.

scholarly journals CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines

2009 ◽  
Vol 11 (1) ◽  
Author(s):  
Gwladys Zabouo ◽  
Anne-Marie Imbert ◽  
Jocelyne Jacquemier ◽  
Pascal Finetti ◽  
Thomas Moreau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Poor Prognosis ◽  
Breast Tumors ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Cd146 Expression

Combination of fulvestrant and lapatinib in non-HER2-overexpressing and adriamycin-resistant breast cancer cell lines

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14050-14050 ◽  
Author(s):  
A. M. Emde ◽  
K. Maslak ◽  
H. Liu ◽  
A. E. Reles ◽  
K. Possinger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Western Blot ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mtt Assay ◽  
Blot Analysis ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells

14050 Background: We evaluated whether combination of lapatinib, a dual tyrosine kinase inhibitor against EGFR and HER2, and fulvestrant, a full estrogen receptor antagonist, is superior in EGFR and HER2 overexpressing and non-overexpressing breast cancer cell lines regarding cell growth inhibition and effects on the protein expression level on special proteins such as PDK1 and ERK1/2. Methods: MTT assay and western blot analysis were performed in the different breast cancer cell lines BT474, T47D, MCF-7 and Adriamycin resistant MCF7 cells. Incubation time was 72h. Concentration of both agents in western blot: 1x10exp-7M, in MTT assay 10exp-11M to 10exp-5M. Results: MTT assay showed a significant stronger proliferation inhibition by lapatinib and fulvestrant in BT474 cells and non- overexpressing T47D cells at a concentration of 10E-7M compared to single agent treatment. By western blot analysis, we found a synergistic downregulation of PDK1 in the combination treatment both in BT474 and AR MCF7 cells, whereas not in T47D cells. In MCF7 cells a downregulation of p-PDK1 was observed after treatment with fulvestrant alone as well as lapatinib plus fulvestrant. Regarding ERK1/2, a synergistic downregulation could be observed in AR MCF7 cells. A downregulation of a p-ERK was detected in MCF-7 cells after treatment with lapatinib, fulvestrant or both. Conclusion: A synergistic action of lapatinib and fulvestrant was observed in all 4 cell lines despite their different receptor status regarding EGFR, HER2 and ER alpha. Shadeo et al. (2005) showed different copy number profiles in these breast cancer cell lines regarding the examined pathways. We could show by western blot analysis that the combination treatment had inhibitory effect on these cell lines according to their individual up-regulated pathways. Altogether, this suggests that the combination is a promising treatment not only in EGFR and HER2 over-expressing breast cancer and that treatment effect is also dependent on up-regulated pathways more likely than receptor status. No significant financial relationships to disclose.

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