Role of LINC01235 on transcriptional output in HCC1954 HER2 positive breast cancer cells
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PROVIDER: PRJNA1132923 | ENA |
REPOSITORIES: ENA
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Project description:LINC01235 plays a crucial role in HER2-positive breast cancer by regulating global histone modifications (H3K27ac, H3K9ac, H3K36me3) and promoting H2A.Z expression in its regulatory regions. It enhances the accessibility of DNA licensing factors at their promoter regions, leading to increased DNA replication and chromosomal instability. These mechanisms contribute to clonal expansion and resistance to anti-HER2 therapies, highlighting LINC01235 as a potential therapeutic target.
2025-07-09 | GSE271688 | GEO
Project description:The intention was to detect genes that are determining trastuzumab efficiency in HER2-positive breast cancer cell lines with different resistance phenotypes. While BT474 should be sensitive to the drug treatment, HCC1954 is expected to be resistant due to a PI3K mutation. The cell line BTR50 has been derived from BT474 and was cultured to be resistant as well. Based on RNA-Seq data, we performed differential expression analyses on these breast cancer cell lines with and without trastuzumab treatment. In detail, five separate tests were performed, namely resistant cells vs. wild type, i.e. HCC1954 and BTR50 vs. BT474, respectively, and untreated vs. drug treated cells. The significant genes of the first two tests should contribute to resistance. The significant genes of the test BT474 vs. its drug treated version should contribute to the trastuzumab effect. To exclude false positives from the combined gene set (#64), we removed ten genes that were also significant in the test BTR50 vs. its drug treated version. This way we ended up with 54 genes that are very likely to determine trastuzumab efficiency in HER2-positive breast cancer cell lines. mRNA profiles of human breast cancer cell lines were generated by deep sequencing using Illumina HiSeq 2000. The cell lines BT474 and HCC1954 were analyzed with and without trastuzumab treatment. HCC1954 is known to be trastuzumab resistant. Additionally, the cell line BTR50 was generated as resistant version of BT474, and was analyzed with and without trastuzumab as well.
2015-04-21 | E-GEOD-55005 | biostudies-arrayexpress
Project description:The intention was to detect genes that are determining trastuzumab efficiency in HER2-positive breast cancer cell lines with different resistance phenotypes. While BT474 should be sensitive to the drug treatment, HCC1954 is expected to be resistant due to a PI3K mutation. The cell line BTR50 has been derived from BT474 and was cultured to be resistant as well. Based on RNA-Seq data, we performed differential expression analyses on these breast cancer cell lines with and without trastuzumab treatment. In detail, five separate tests were performed, namely resistant cells vs. wild type, i.e. HCC1954 and BTR50 vs. BT474, respectively, and untreated vs. drug treated cells. The significant genes of the first two tests should contribute to resistance. The significant genes of the test BT474 vs. its drug treated version should contribute to the trastuzumab effect. To exclude false positives from the combined gene set (#64), we removed ten genes that were also significant in the test BTR50 vs. its drug treated version. This way we ended up with 54 genes that are very likely to determine trastuzumab efficiency in HER2-positive breast cancer cell lines.
2015-04-21 | GSE55005 | GEO
Project description:Lymph node status is a crucial predictor for the overall survival of invasive breast cancer. However, lymph node involvement is only detected in about half of HER2 positive patients. Currently, there are no biomarkers available for distinguishing small size HER2-positive breast cancers with different lymph node statuses. Thus, in the present study, we applied label-free quantitative proteomic strategy to construct plasma proteomic profiles of ten patients with small size HER2-positive breast cancers (5 patients with lymph node metastasis versus 5 patients with lymph node metastasis).
2018-02-08 | PXD007217 | Pride
Project description:The goal of our study is to build an integrated transcriptome landscape model for HER2 positive breast tumors and identify the crucial signaling pathways associated with HER2 tumors. Genomic features include, 685 genes that were differentially expressed only in HER2-positive tumors, 102 genes that were alternatively spliced in a pattern that is unique to HER2-positive tumors, and 303 genes that expressed single nucleotide sequence variants (eSNVs) that were unique to HER2-positive tumors. Network analysis was performed to integrate the genomic features into a transcriptome landscape model that identified 12 highly interconnected cellular processes that appear to be critical to the establishment and maintenance of HER2-positive tumors. We observed that integrin signaling was linked to lapatinib sensitivity in vitro and strongly associated with risk of relapse in the NCCTG N9831 adjuvant trastuzumab clinical trial dataset. We analyzed RNA-seq data from a survey panel consisting of 8 benign breast lesions, 8 ER+, 8 triple negative, and 8 HER2-positive primary breast tumors to identify genomic features that were uniquely associated with HER2-positive tumors
2013-12-06 | E-GEOD-45419 | biostudies-arrayexpress
Project description:The use of trastuzumab and pertuzumab in combination with docetaxel for initial treatment of HER2-positive breast cancer patients has resulted in notable clinical benefits in comparison to docetaxel administered with trastuzumab alone. Nevertheless, although therapeutic success is evident at the outset, the majority of tumours eventually advance, rendering metastatic disease and subsequent recurrence in patients who have developed acquired resistance. There is an urgent requirement to enhance our comprehension of the mechanisms governing resistance, enabling us to develop targeted therapeutic approaches to improve efficacy. We produced four HER2-positive-derived cell lines through prolonged exposure to trastuzumab and pertuzumab, determining their resistance rates. We confirmed long-term resistance through a notable increase in colony formation capacity of the derived cells. We confirmed the molecular identity of the new cell lines using immunohistochemistry of their receptors and profiling of point mutations. We detected HER2 overexpression in all cell lines and resistance to trastuzumab and pertuzumab did not result in variations in ER, PR and HER2 receptor expression. Finally, a study using proteomics analysis confirmed a significant alteration in the abundance patterns of over 600 proteins. This has implications for various vital biological processes such as ribosome creation, mitochondrial functionality, and metabolism. These mechanisms may play a crucial role in developing resistance in HER2-positive breast cancer. We conclude that these BCCLs resistant to trastuzumab plus pertuzumab-based anti-HER2 therapy could be a useful resource to enhance comprehension of resistance acquisition mechanisms.
2024-01-26 | PXD045804 | Pride
Project description:Abstract: A subset of HER2 breast cancers with amplification of the TFAP2C gene locus becomes addicted to AP-2g. We sought to define AP-2g-regulated genes that control growth and invasiveness by comparing HER2 cell lines with differential response to TFAP2C knockdown. A set of 68 differentially expressed genes was identified, which included CDH5 and CDKN1A. Pathway analysis implicated the MAPK13/p38δ and retinoic acid regulatory nodes, which were confirmed to display divergent responses. The AP-2g gene signature was highly predictive of outcome in HER2-positive breast cancer patients. We conclude that AP-2g regulates a set of genes in HER2 breast cancer that drive cancer growth and invasiveness and that the AP-2g gene signature can predict outcome of patients with HER2 breast cancer. Results: Using an optimized data analysis workflow, we mapped about 50-75 million sequence reads per sample to the human genome Human Feb.2009 (GRCh37/hg19) (hg19). By RNA-seq analysis, knockdown of TFAP2C in HCC1954 with siRNA (compared to NT siRNA) identified 364 genes with significantly altered expression. To further create specificity for AP-2gamma-regulated genes, RNA-seq analysis was performed comparing expression in shHCC1954 with shTFAP2C cells vs. shNT; this analysis identified 8,986 genes with significantly altered expression. The two data sets were subsequently compared to identify a set of genes that were consistently altered with knockdown of TFAP2C by siRNA and shRNA. This comparison confirmed the identification of 152 AP-2gamma target genes in HCC1954 cells. Because HCC1954 demonstrated opposite growth regulation and invasiveness with knockdown of TFAP2C compared to SKBR3, we hypothesized that the AP-2gamma target genes responsible for growth and invasion would be differentially regulated with knockdown of TFAP2C in HCC1954 versus SKBR3. Hence, RNA-seq analysis was performed in SKBR3 after knockdown of TFAP2C with siRNA; in this analysis, a total of 3814 genes were significantly altered. The pattern of expression for the 152 AP-2gamma target genes identified in HCC1954 was subsequently compared to expression changes in SKBR3. Of note, only 79 of the 152 TFAP2C target genes in HCC1954 were found to change expression significantly in the RNA-seq data set from SKBR-3. Conclusions: Knockdown of TFAP2C with co-knockdown of CDH5 in SKBR-3 confirmed no significant effect on invasion, though there was a slight reduction in invasiveness with knockdown of CDH5 that failed to reach statistical significance (p=0.12). These findings support the conclusion that regulation of CDH5 and CDKN1A contribute to alterations of proliferation and invasiveness induced by knockdown of TFAP2C.
2020-04-13 | GSE126894 | GEO
Project description:Conditioned medium experiments carried out in our laboratory with CAFs derived from HER2-positive patients showed a significant capacity to promote resistance to trastuzumab plus pertuzumab therapies in two HER2-positive breast cancer cell lines (BCCLs), even in the presence of docetaxel. In order to elucidate the components of CAF-conditioned medium that would be relevant in the promotion of BCCL resistance, we performed a multi-omics strategy to identify miRNAs, cytokines, transcription factors and/or kinases in the secretome that target specific objectives in cancer cells. The combination of miRNA analysis, label-free LC-MS/MS quantification and cytokine arrays to explore the secretome of CAFs under treatment conditions revealed several up- and down-regulated candidates. We discuss the potential role of some of the most interesting candidates in generating resistance in HER2-positive breast cancer
2022-01-26 | PXD025556 | Pride
Project description:Advancing precision medicine in the field of cancer is still curbed by the fact that a rational basis to predict treatment outcome is missing. To unravel the mechanism behind targeted drugs (trastuzumab, pertuzumab, erlotinib), mathematical modeling employing ordinary differential equations (ODE) was combined with wet-lab experimentation. Experimentation relied on systematic perturbation experiments to monitor the signaling-response towards drugs in the context of EGF signaling in the HER2+ cell lines SKBR3 and HCC1954.
2016-12-31 | GSE55891 | GEO
Project description:The goal of our study is to build an integrated transcriptome landscape model for HER2 positive breast tumors and identify the crucial signaling pathways associated with HER2 tumors. Genomic features include, 685 genes that were differentially expressed only in HER2-positive tumors, 102 genes that were alternatively spliced in a pattern that is unique to HER2-positive tumors, and 303 genes that expressed single nucleotide sequence variants (eSNVs) that were unique to HER2-positive tumors. Network analysis was performed to integrate the genomic features into a transcriptome landscape model that identified 12 highly interconnected cellular processes that appear to be critical to the establishment and maintenance of HER2-positive tumors. We observed that integrin signaling was linked to lapatinib sensitivity in vitro and strongly associated with risk of relapse in the NCCTG N9831 adjuvant trastuzumab clinical trial dataset.
2013-12-06 | GSE45419 | GEO