Differential gene expression analysis on 24 arrays derived from the human HAC15 cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE140818 | GEO | 2020/01/20
REPOSITORIES: GEO
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Project description:A previous case study described an adrenal incidentaloma initially misdiagnosed as adrenocortical carcinoma (ACC) and treated with mitotane. The final diagnosis was metastatic melanoma of unknown primary origin. However, the patient developed rapid disease progression after mitotane withdrawal, suggesting a protective role for mitotane in a non-adrenal derived tumour. The aim of the present study was to determine the biological response of primary melanoma cells obtained from that patient and in two other established melanoma and ACC cell lines treated with mitotane. Although mitotane inhibited proliferation of both ACC and melanoma cells, its role in melanoma treatment appears to be limited. Flow cytometry analysis and transcriptomic studies indicated that the ACC cell line was highly responsive to mitotane treatment, although the primary melanoma cell line showed a moderate response in vitro. Mitotane modified activity in several key biological processes, including “mitotic nuclear division”, “DNA repair”, “angiogenesis”, and “negative regulation of ERK1 and ERK2 cascade”.
2021-11-02 | GSE186870 | GEO
Project description:The actual drug treatment options for adrenocortical carcinoma (ACC) are rather narrow and intensive efforts are going on to find novel effective agents. In our previous functional genomics study, retinoid signaling via the retinoid X receptor (RXR) was detected as a major pathogenic pathway in ACC and we have demonstrated the in vitro activity of 9-cis retinoic acid (9-cisRA) acting via the RXR on NCI-H295R cells and also found that 9-cisRA has antitumoral effects in a small pilot xenograft study. In the present study our aim was to confirm the antitumoral effect of 9-cisRA on adrenocortical cancer in a large xenograft study involving both mitotane and 9-cisRA and their combination. 43 male SCID mice inoculated with NCI-H295R cells were treated in four groups (i. control – corn oil vehicle, ii. 5 mg/kg 9-cisRA, iii. 200 mg/kg mitotane, iv. 5 mg/kg 9-cisRA + 200 mg/kg mitotane) for 28 days. Regular tumor size follow-up, histological and immunohistochemical (Ki-67) analysis, tissue gene expression microarray have been performed. Quantitative real-time-PCR was used for the validation of the microarray results and to detect circulating and tissue microRNAs. To examine the proteome proteomics and Western-blot analysis were executed. We have found that both 9-cisRA and mitotane reduced tumor growth relative to control, but only the combination of the two agents resulted in significant tumor size reduction. The Ki-67 index was significantly reduced in both 9-cisRA and 9-cisRA+mitotane groups. Gene expression analysis revealed 483 genes with significant differences in expression, but only without Benjamini-Hochberg correction (APOA4 and PDE4A were validated).
2016-06-07 | GSE73417 | GEO
Project description:<p>We analyzed clonal evolution in serial samples from five CLL patients who became resistant to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, using whole-exome and deep targeted sequencing. We observe a BTK-C481S mutation in one of five patients, and multiple PLCG2 mutations in a second patient. The other patients had an expansion of clones harboring del(8p) carrying additional driver mutations (EP300, MLL2, EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. We calculated the growth kinetics of ibrutinib-resistant subclones and estimated the size of the resistant clones at treatment initiation, which we validated by droplet-microfluidic technology. Haplo-insufficiency of TRAIL-R, a consequence of del(8p), led to TRAIL insensitivity which may contribute to development of ibrutinib resistance. These findings demonstrate that ibrutinib therapy has the potential to lead to clonal selection and expansion of rare cell populations already present at the time of treatment initiation. They also provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance, previously attributed solely to mutations in BTK and related pathway molecules.</p>
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Project description:The extent of intratumoral heterogeneity, the subclonal structures and the mechanisms of treatment-induced clonal selection by cisplatin was investigated in the squamous cell carcinoma cell line model FaDu. We picked 96 single cell-derived clones from the cisplatin-sensitive parental FaDu cell line. After expansion as separate cultures, these clones were tested for their sensitivity to CDDP. By this approach, we isolated individual cell clones that were primarily resistant (clones 5 & 78) and others that showed high sensitivity to CDDP (clones 46 & 54). Basal mRNA expression levels associated with CDDP sensitivity / resistance were determined in two independent microarray analyses.
2017-12-04 | E-MTAB-6022 | biostudies-arrayexpress
Project description:The actin-bundling protein fascin (FSCN1) is overexpressed in aggressive adrenocortical carcinoma (ACC) and represents a reliable prognostic indicator. We investigated the effects of FSCN1 inactivation by CRISPR/Cas9 in ACC H295R cells on global gene expression profiles in those cells. We performed gene expression profiling analysis using data obtained from RNA-seq of 2 different H295R control clones and 2 different FSCN1 KO clones (2 biological replicates for each clone).
2022-10-25 | GSE216008 | GEO
Project description:Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic alterations. This results in phenotypic and molecular heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We aimed at dissecting the molecular mechanisms underlying the cooperation between different clones. We produced clonal cell lines derived from the MDA-MB-231 breast cancer cell line, using the UbC-StarTrack system, which allows tracking of multiple clones by colour: GFP C3, mKO E10 and Sapphire D7. Characterization of these clones in vitro revealed clear differences at genetic levels, that induce differences in growth rate, morphology and cytokine expression among them. In vivo, all clonal cell lines were able to form tumors, however an injection of an equal mix of clones, led to the formation of tumors where mKO E10 was almost depleted. Additionally, the mKO E10 clonal cell line showed a significant deficiency in the formation of lung metastasis. These results confirm that even in stable cell lines heterogeneity is present. In vitro the complementation of growth medium with medium or exosomes from either parental or clonal cell lines, increased the growth rate of the other clones. Co-growth and co-injection of mKO E10 and GFP C3 clonal cell lines increased the efficiency of invasion and migration, respectively. These findings support a model where the interplay of clones confers aggressiveness and may allow to identify factors involved in cellular communication which can be involved in clonal cooperation and be new targets preventing tumor progression.
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Project description:<p>Hematopoietic stem cell (HSC) mutations can result in clonal hematopoiesis (CH) with heterogeneous clinical outcomes. Here, we investigated how the cell state preceding <em>Tet2</em> mutation impacts the pre-malignant phenotype. Using an inducible system for clonal analysis of myeloid progenitors, we found that the epigenetic features of clones at similar differentiation status were highly heterogeneous and functionally responded differently to <em>Tet2</em> mutation. Cell differentiation stage also influenced <em>Tet2</em> mutation response indicating that the cell of origin's epigenome modulates clone-specific behaviors in CH. Molecular features associated with higher risk outcomes include <em>Sox4</em> that sensitized cells to <em>Tet2</em> inactivation, inducing dedifferentiation, altered metabolism and increasing the <em>in vivo</em> clonal output of mutant cells, as confirmed in primary GMP and HSC models. Our findings validate the hypothesis that epigenetic features can predispose specific clones for dominance, explaining why identical genetic mutations can result in different phenotypes.</p>
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Project description:Human ACC cell-line NCI-H295 was treated in biological triplicate for 6 hours with 50M-eM-5M (16 mg/l) and 100M-eM-5M (32 mg/l) mitotane or diluent as control.Genome-wide gene expression analyses were performed using the Affymetrix HG_133_plus2 array to identify the molecular mechanisms underlying mitotane action in an unsupervised fashion.
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