Next genereration sequencing reveals that CNAs associated with cyclin E overexpression tranlate into changes in transcriptional output.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE136078 | GEO | 2020/08/30
REPOSITORIES: GEO
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Project description:Cyclin E, a key cell cycle regulatory protein, has been linked to oncogenesis when dysregulated. We have previously shown that overexpression of cyclin E causes replication stress, leading to failure to complete replication at specific chromosomal loci during S phase of the cell cycle. This, in turn promotes chromosomal damage during anaphase. Here we show that non-transformed human mammary epithelial cell clones that survive such aberrant mitoses, have a specific and reproducible pattern of chromosomal Copy Number Alterations (CNAs) that we have characterized and termed the cyclin E CNA signature. Using a number of computational approaches, we show that this signature resembles one specific CNA pattern enriched in differentiated epithelial-like tumors of the breast and ovary. We further show that this CNA signature translates into expected altered patterns of transcription. In addition, we show that 2 out of 12 clones analyzed were capable of anchorage-independent growth, suggesting acquisition of sufficient oncogenic transformation properties. Analysis of the CNA profile of these clones provides a potential mechanism for cyclin E-mediated oncogenesis.
2019-08-25 | GSE136297 | GEO
Project description:Next genereration sequencing reveals that CNAs associated with cyclin E overexpression tranlate into changes in transcriptional output.
| PRJNA561187 | ENA
Project description:Analysis of mammary glands from tet-inducible(rtTA) transgenic mice expressing cyclin D1 using Affymetrix Mouse Gene 1.0 ST GeneChip arrays. MMTV-rtTA transgenic mice (MMTV-Mouse Mammary Tumor Virus promoter) were cross-mated to cyclin D1 transgenic mice under control of tet operon. 8-week-old tetracycline-inducible cyclin D1/rtTA bi-transgenic pregnant female mice (12 days postcoitus) were treated with doxycycline through drinking water supplementation at a final concentration of 2 mg/ml. Control mice were rtTA transgenics alone and treated in the same manner. After 7 days of doxycycline treatment, the mice were sacrificed and mammary glands taken for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 through acute induction. Analysis of mammary glands from MMTV-cyclin D1/WT and MMTV-cyclin D1/KE using Affymetrix Mouse 430A v2.0 GeneChip arrays. Cyclin D1 point mutant, cyclin D1/KE K112E (K112E) contains a lysine to glutamine substitution at amino acid position 112. cyclin D1. The cyclin D1/KE mutant fails to induce cyclin D1-dependent kinase activity. Female MFD1, MFD1-KE, and WT mice were monitored twice weekly, up to 760 days, for the development of palpable tumors. Those developing palpable tumors were sacrificed within a week of tumor detection. Tumors were dissected and portions snap frozen for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 that is kinase independent.
2013-12-31 | GSE43216 | GEO
Project description:Analysis of mammary glands from tet-inducible(rtTA) transgenic mice expressing cyclin D1 using Affymetrix Mouse Gene 1.0 ST GeneChip arrays. MMTV-rtTA transgenic mice (MMTV-Mouse Mammary Tumor Virus promoter) were cross-mated to cyclin D1 transgenic mice under control of tet operon. 8-week-old tetracycline-inducible cyclin D1/rtTA bi-transgenic pregnant female mice (12 days postcoitus) were treated with doxycycline through drinking water supplementation at a final concentration of 2 mg/ml. Control mice were rtTA transgenics alone and treated in the same manner. After 7 days of doxycycline treatment, the mice were sacrificed and mammary glands taken for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 through acute induction. Analysis of mammary glands from MMTV-cyclin D1/WT and MMTV-cyclin D1/KE using Affymetrix Mouse 430A v2.0 GeneChip arrays. Cyclin D1 point mutant, cyclin D1/KE K112E (K112E) contains a lysine to glutamine substitution at amino acid position 112. cyclin D1. The cyclin D1/KE mutant fails to induce cyclin D1-dependent kinase activity. Female MFD1, MFD1-KE, and WT mice were monitored twice weekly, up to 760 days, for the development of palpable tumors. Those developing palpable tumors were sacrificed within a week of tumor detection. Tumors were dissected and portions snap frozen for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 that is kinase independent. Two separate control mice were positive for MMTV-rtTA transgene compared to 3 separate cyclin D1/rtTA bitransgenic female mice and 3 separate cyclin D1 KE mutant/rtTA bitransgenic female mice (Mouse Gene 1.0 ST arrays). Three separate control WT FvBmice were compared to three MMTV-cyclin D1/WT and 3 MMTV-cyclin D1/KE mice (Mouse 430A v2.0 arrays).
2013-12-31 | E-GEOD-43216 | biostudies-arrayexpress
Project description:Yeast cells were arrested either in G1 (for CLN3 overexpression) or in G2/M (for CLB2 overexpression). The cyclin was then induced, and samples were taken. This study is described in more detail in Spellman PT et al.(1998) Mol Biol Cell 9:3273-97 Keywords: other
2002-02-12 | GSE25 | GEO
Project description:Analysis of mammary glands from tet-inducible (rtTA) transgenic mice expressing cyclin D1 (Ccnd1). MMTV-rtTA transgenic mice (MMTV-Mouse Mammary Tumor Virus promoter) were cross-mated to cyclin D1 transgenic mice under the control of the tet operon. 8-week-old tetracycline-inducible cyclin D1/rtTA bi-transgenic pregnant female mice (12 days postcoitus) were treated with doxycycline through drinking water supplementation at a final concentration of 2 mg/ml. Control mice were rtTA transgenics alone and were treated in the same manner. After 7 days of doxycycline treatment, the mice were sacrificed and mammary glands taken for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 through acute induction.
2012-02-10 | GSE35076 | GEO
Project description:Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm characterized by the t(11;14)(q13;q32) translocation leading to cyclin D1 overexpression. Cyclin D1 is a major cell cycle regulator and also has a role in transcription, but the effect of the latter in tumorigenesis remains largely unknown. Here, we investigated the transcriptional role of cyclin D1 in MCL and its impact on the pathogenesis of this neoplasm. Integrating genome-wide expression analysis of cyclin D1-silenced and overexpressing cells with cyclin D1 chromatin binding profiles, we identified a cyclin D1-activated transcriptional program in MCL cells. We used microarrays to analyze the genome-wide expression modulation in cyclin D1 overexpression models established in the cyclin D1-negative lymphoblastoid cell line JVM13.
2021-06-30 | GSE144095 | GEO
Project description:Analysis of mammary glands from tet-inducible (rtTA) transgenic mice expressing cyclin D1 (Ccnd1). MMTV-rtTA transgenic mice (MMTV-Mouse Mammary Tumor Virus promoter) were cross-mated to cyclin D1 transgenic mice under the control of the tet operon. 8-week-old tetracycline-inducible cyclin D1/rtTA bi-transgenic pregnant female mice (12 days postcoitus) were treated with doxycycline through drinking water supplementation at a final concentration of 2 mg/ml. Control mice were rtTA transgenics alone and were treated in the same manner. After 7 days of doxycycline treatment, the mice were sacrificed and mammary glands taken for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 through acute induction. Two separate control mice positive for the MMTV-rtTA transgene were compared to 3 separate cyclin D1/rtTA bi-transgenic female mice.
2012-02-10 | E-GEOD-35076 | biostudies-arrayexpress
Project description:CytoScan HD array data from Human mammary epithelian cells after Cyclin E overexpression
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Project description:Tumor recurrence represents a significant clinical challenge in the treatment and management of breast cancer. To investigate whether copy number aberrations (CNAs) facilitate the re-emergence of tumor growth from residual disease we performed array comparative genomic hybridization (aCGH) on primary and recurrent mammary tumors from an inducible mouse model of type-I insulin-like growth factor receptor (IGF-IR) driven breast cancer. This genome-wide analysis revealed primary and recurrent tumors harbored distinct copy number aberrations (CNAs) with relapsed tumors containing an increased number of gene-level gains and losses. Remarkably, CNAs detected in primary tumors were largely devoid of annotated cancer genes while the vast majority of recurrent tumors harbored at least one CNA containing a known oncogene or tumor suppressor. Specifically, a subset of recurrent tumors carried gains at 6qA2 and 9qA2 which encode the Met and Yap1 oncogenes respectively. The most frequent CNA detected was a focal deletion at 4qC5 involving the Cdkn2a and Cdkn2b tumor suppressor genes. Integrative analysis revealed positive correlations between gene copy number and mRNA expression suggesting Met, Yap1 and Cdkn2a/b may serve as potential driver genes that promote tumor recurrence. Together, these findings indicate that tumor recurrence is facilitated by the acquisition of CNAs with oncogenic potential and provide a framework to dissect the molecular mechanisms that mediate tumor escape from dormancy.
2018-11-28 | GSE120186 | GEO