MicroRNAome of highly metastatic and non-metastatic human breast cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Wang Yanfang
PROVIDER: S-ECPF-GEOD-17350 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:MicroRNAs are noncoding, endogenous small RNAs that regulate target genes by cleavage of the targeted mRNA or translational repression. We investigated the microRNAome using 2-color microarrays in a highly invasive human breast cancer cell line, MDA-MB-231 (sub line 4175) and a non-invasive breast epithelial cell line, MCF10A. We found 13 miRNAs that were up-regulated and 9 were down-regulated significantly in 4175 cells (p <0.05, fold change >2) compared with MCF10A cells.
2009-07-28 | GSE17350 | GEO
Project description:MicroRNAs are noncoding, endogenous small RNAs that regulate target genes by cleavage of the targeted mRNA or translational repression. We investigated the microRNAome using 2-color microarrays in a highly invasive human breast cancer cell line, MDA-MB-231 (sub line 4175) and a non-invasive breast epithelial cell line, MCF10A. We found 13 miRNAs that were up-regulated and 9 were down-regulated significantly in 4175 cells (p <0.05, fold change >2) compared with MCF10A cells. We compared the highly metastatic human breast cell lines MDA-MB-231 (4175 subline) with non-metastatic MCF10A cell lines. Two 4175 sublines and two MCF10A cell lines, independently grown and harvested. Dye swap was performed.
2010-05-15 | E-GEOD-17350 | biostudies-arrayexpress
Project description:BACKGROUND/PURPOSE:TrkA overexpression occurs in over 20% of breast cancers, including triple-negative breast cancers (TNBC), and has recently been recognized as a potential driver of carcinogenesis. Recent clinical trials of pan-Trk inhibitors have demonstrated targeted activity against tumors harboring NTRK fusions, a relatively rare alteration across human cancers. Despite this success, current clinical trials have not investigated TrkA overexpression as an additional therapeutic target for pan-Trk inhibitors. Here, we evaluate the cancerous phenotypes of TrkA overexpression relative to NTRK1 fusions in human cells and assess response to pharmacologic Trk inhibition. EXPERIMENTAL DESIGN/METHODS:To evaluate the clinical utility of TrkA overexpression, a panel of TrkA overexpressing cells were developed via stable transfection of an NTRK1 vector into the non-tumorigenic breast cell lines, MCF10A and hTERT-IMEC. A panel of positive controls was generated via stable transfection with a CD74-NTRK1 fusion vector into MCF10A cells. Cells were assessed via various in vitro and in vivo analyses to determine the transformative potential and targetability of TrkA overexpression. RESULTS:TrkA overexpressing cells demonstrated transformative phenotypes similar to Trk fusions, indicating increased oncogenic potential. TrkA overexpressing cells demonstrated growth factor-independent proliferation, increased PI3Kinase and MAPKinase pathway activation, anchorage-independent growth, and increased migratory capacity. These phenotypes were abrogated by the addition of the pan-Trk inhibitor, larotrectinib. In vivo analysis demonstrated increased tumorgenicity and metastatic potential of TrkA overexpressing breast cancer cells. CONCLUSIONS:Herein, we demonstrate TrkA overexpressing cells show increased tumorgenicity and are sensitive to pan-Trk inhibitors. These data suggest that TrkA overexpression may be an additional target for pan-Trk inhibitors and provide a targeted therapy for breast cancer patients.
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Project description:Triple-negative breast cancer (TNBC) is a group of cancer with high diversity, limited therapies, and poor prognosis. TNBC cell lines and animal models provide effective tools for studies and drug discovery. Here, we report the development of two TNBC cell lines (XtMCF and LmMCF) based on our existing cell model that consists of normal breast epithelial cell line MCF10F, estradiol-transformed cells trMCF, and Boyden chamber-selected tumorigenic cells bsMCF. The XtMCF and LmMCF cell line were derived from xenograft and lung metastasis of bsMCF cells, respectively. The bsMCF, XtMCF, and LmMCF cells have undergone epithelial-mesenchymal transition (EMT), exhibiting a mesenchymal-like feature. In vivo studies showed XtMCF and LmMCF cells were highly tumorigenic and metastatic. The injection of 5 × 10(4) cells to CB17/SCID mice mammary fat pad produced xenografts in 9/9 mice and tumors reached 10 millimeters in diameter in 5 weeks. The injection of 1 × 10(6) XtMCF or 8 × 10(4) LmMCF cells into the mice tail vein was sufficient to form extensive lung metastases in 4 weeks. The two new cell lines exhibited CD44(+) /CD49f(+) and CD44(+) /EpCAM(+) cancer stem cell (CSC) characteristics, and the EGF-like domain of EpCAM was cleaved off. Together with the normal and early transformed counterparts, herein we provide a complete cancer model for the study of initiation, evolution, and identification of new therapeutics for TNBC. The finding that EGF-like domain of EpCAM was cleaved off in cells which have undergone EMT suggests this cleavage may be involved in the EMT process and the cancer stem cell properties of these cells.
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Project description:The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to phorbol 12-myristate 13-acetate (PMA). In sensitive cells, PMA causes Erk MAPK activation and Erk-mediated growth arrest. In resistant cells, PMA induces a low level of Erk activation, without growth arrest. A relatively unexplored aspect of the phenotypes is that resistant cells are more adherent to culture substrate than are sensitive cells. In this study, the roles of the protein tyrosine kinases FAK and Pyk2 in EL4 phenotype were examined, with a particular emphasis on the role of these proteins in metastasis. FAK is expressed only in PMA-resistant (or intermediate phenotype) EL4 cells, correlating with enhanced cell-substrate adherence, while Pyk2 is more highly expressed in non-adherent PMA-sensitive cells. PMA treatment causes modulation of mRNA for FAK (up-regulation) and Pyk2 (down-regulation) in PMA-sensitive but not PMA-resistant EL4 cells. The increase in Pyk2 mRNA is correlated with an increase in Pyk2 protein expression. The roles of FAK in cell phenotype were further explored using transfection and knockdown experiments. The results showed that FAK does not play a major role in modulating PMA-induced Erk activation in EL4 cells. However, the knockdown studies demonstrated that FAK expression is required for proliferation and migration of PMA-resistant cells. In an experimental metastasis model using syngeneic mice, only FAK-expressing (PMA-resistant) EL4 cells form liver tumors. Taken together, these studies suggest that FAK expression promotes metastasis of EL4 lymphoma cells.
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