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Mcl-1 is a key determinant of breast cancer cell survival [expression]

ABSTRACT: mRNA expression profile of cultured Breast Cancer cell line measured by Affymetrix microarrays Whole genome expression profile of 32 breast cancer cell lines were analyzed with 3 biological replicates.

ORGANISM(S): Homo sapiens

SUBMITTER: Xin Lu

PROVIDER: E-GEOD-66071 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MCL-1 Is a Key Determinant of Breast Cancer Cell Survival: Validation of MCL-1 Dependency Utilizing a Highly Selective Small Molecule Inhibitor.

Xiao Yu Y Nimmer Paul P Sheppard George S GS Bruncko Milan M Hessler Paul P Lu Xin X Roberts-Rapp Lisa L Pappano William N WN Elmore Steven W SW Souers Andrew J AJ Leverson Joel D JD Phillips Darren C DC

Molecular cancer therapeutics 20150526 8

Hyperexpression of antiapoptotic BCL-2 family proteins allows cells to survive despite the receipt of signals that would ordinarily induce their deletion, a facet frequently exploited by tumors. Tumors addicted to the BCL-2 family proteins for survival are now being targeted therapeutically. For example, navitoclax, a BCL-2/BCL-XL/BCL-W inhibitor, is currently in phase I/II clinical trials in numerous malignancies. However, the related family member, MCL-1, limits the efficacy of navitoclax and ...[more]

PMID: 26013319

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Mcl-1 is a key determinant of breast cancer cell survival [copy number]

Project description:Copy number profile of cultured Breast Cancer cell line measured by Affymetrix SNPs microarrays Whole genome copy number profile of 2 breast cancer cell lines were analyzed using Affymetrix SNP6.0 arrays

2015-08-07 | E-GEOD-66070 | biostudies-arrayexpress

Mcl-1 is a key determinant of breast cancer cell survival

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-08-07 | E-GEOD-66072 | biostudies-arrayexpress

Mcl-1 is a key determinant of breast cancer cell survival [expression]

Project description:mRNA expression profile of cultured Breast Cancer cell line measured by Affymetrix microarrays

2015-08-07 | GSE66071 | GEO

Mcl-1 is a key determinant of breast cancer cell survival [copy number]

Project description:Copy number profile of cultured Breast Cancer cell line measured by Affymetrix SNPs microarrays

2015-08-07 | GSE66070 | GEO

Identification of a tumor suppressor network in T-cell leukemia.

Project description:In T-cell acute lymphoid leukemia (T-ALL) several oncogenes and tumour suppressor (TS) genes have been described. Deregulation of these genes mostly results from genomic aberrations, including translocations, amplifications and deletions. To identify novel cancer-related genes targeted by copy number alterations we performed genomic profiling of eight T-ALL cell lines. In three of these (HPB-ALL, JURKAT, MOLT-14) we identified a shared deletion at chromosomal position 2p16.3-p21. Within the minimally deleted region we recognized several candidate TS genes, including FBXO11 (component of the ubiquitin-pathway) and FOXN2 (developmental transcription factor). Furthermore, an additional deletion at 14q23.2-q32.11 (in cell line RPMI-8402) included FOXN3, highlighting this class of FOX genes as potential TS. Accordingly, quantitative expression analyses of FBXO11, FOXN2 and FOXN3 confirmed reduced transcript levels in the indicated cell lines. Moreover, reduced expression of these genes was also observed in about 7 % of T-ALL patients from a public dataset (GSE26713), showing their clinical relevance in this malignancy. Bioinformatic analyses of these patient data revealed concurrent reduction of FOXN2 and/or FOXN3 together with homeobox gene ZHX1. Consistently, knockdown experiments and reporter gene assays demonstrated that both FOXN2 and FOXN3 directly activated transcription of ZHX1 in T-ALL. ZHX1 target gene analysis via expression profiling after siRNA-mediated knockdown indicated regulation of several genes involved in the ubiquitin-pathway including CUL4A. Taken together, we identified novel TS genes which form a regulatory network improving our understanding of T-cell development and leukemogenesis.

2017-02-01 | E-MTAB-5232 | biostudies-arrayexpress

Mcl-1 is a key determinant of breast cancer cell survival

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-08-07 | GSE66072 | GEO

Basal gene expression data of 21 cell lines (18 cancer and 3 non-tumorigenic)

Project description:We profiled basal gene expressed levels of 21 cell lines (18 cancer and 3 non-tumorigenic) using Affymetrix HG-U133_plus2 GeneChip microarrays. Goal of the experiment was to benchmark a number of algorithms for biomarker detection all of which utilize gene expression data. Cell lines were cultivated in appropriate media according to supplier recommendations. Goal was to acquire a basal gene expression profile of 21 common cell lines.

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MCL1 inhibitor induces apoptosis in Anaplastic Large Cell Lymphoma and in Primary Effusion Lymphoma

Project description:Overexpression of antiapoptotic BCL2 family proteins occurs in various hematologic malignanices and contributes to leukemogenesis by inhibiting the apoptotic machinery of the cells. BH3 mimetics provide an option for medication, with venetoclax as the first drug applied for chronic lymphocytic leukemia and for acute myeloid leukemia. To find additional hematologic entities with ectopic expression of BCL2 family members, we performed expression screening applying the LL-100 panel. Primary effusion lymphoma (PEL) and anaplastic large cell lymphoma (ALCL), 2/22 entities covered by this panel, stood out by high expression of MCL1 and low expression of BCL2. The MCL1 inhibitor AZD-5991 induced apoptosis in both malignancies suggesting that this BH3 mimetic might be efficient as drug for these diseases. The ALCL cell lines also expressed BCLXL and BCL2A1, both contributing to survival of the cells. The combination of specific BH3 mimetics yielded synergistic effects, pointing to a novel strategy for the treatment of ALCL. The PI3K/AKT inhibitor BEZ-235 could also efficiently be applied in combination with AZD-5991, providing an alternative to avoid thrombocytothemia, which is associated with the use of BCLXL inhibitors.

2021-12-31 | E-MTAB-10903 | biostudies-arrayexpress

Expression data from breast tumors in different age-specific cohorts and for different sequentional disease stages

Project description:Compared transccriptome of breast cancer in young women to those arising in two mature groups to characterize the underlying biological mechanisms of the breast cancer in Middle Eastern young women. Also, compared the gene expression profile characteristic of the sequential disease stages (ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC)) of breast cancer to elucidate the molecular mechanisms of breast cancer progression in young women. Analyzed the whole-genome mRNA expression profile from tumor (n=73) and adjacent disease free tissues (n=36) using Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays.

2014-08-01 | E-GEOD-29044 | biostudies-arrayexpress

Fine-scale mapping of copy-number alterations with massively parallel sequencing

Project description:In order to benchmark the reproducibility of Affymetrix 238K Sty arrays for detecting copy-number alterations. We performed replicate hybridizations of 3 tumor cell lines and 2 paired normal cell lines obtained from the American Type Culture Collection (ATCC). We calculated copy numbers at each SNP probeset by array pre-processing with the GISTIC algorithm (PMID: 18077431). For each SNP probeset, we calculated the median copy number across replicate arrays. The median copy number profile for each tumor cell line was segmented with the GLAD algorithm (PMID: 15381628) to partition the genome into regions of constant copy number. We compared the copy-number alterations detected by GLAD segmentation of these arrays with statistical analyses of short sequence reads obtained from the Illumina/Solexa 1G GenomeAnalyzer. Shotgun sequencing results can be found in the NCBI Short Read Archive, accession number SRP000246. Keywords: disease state analysis 77 replicates of HCC1143 (breast ductal carcinoma), 69 replicates of HCC1143BL (matched normal), 42 replicates of HCC1954 (breast ductal carcinoma), 36 replicates of HCC1954BL (matched normal), 1 replicate of NCI-H2347 (lung adenocarcinoma)

2008-11-13 | E-GEOD-12019 | biostudies-arrayexpress

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