GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE35494 Query DataSets for GSE35494
Status Public on Feb 02, 2012
Title Control shRNA- vs. obscurin shRNA-expressing MCF10A cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Obscurins (~70-870kDa), encoded by the single OBSCN gene, are cytoskeletal proteins originally identified in striated muscles with structural and regulatory roles. Recently, analysis of 13,023 genes in breast and colorectal cancers identified OBSCN as one of the most frequently mutated genes, implicating it in cancer formation. Herein, we studied the expression profile of obscurins in breast, colon and skin cancer cell lines, and their involvement in cell survival. Immunoblot analysis demonstrated significant reduction of obscurins in cancer cells, resulting from decreased mRNA levels and/or the presence of mutant transcripts. In normal epithelium, obscurins localize in cytoplasmic puncta, the cell membrane and the nucleus. Accordingly, subcellular fractionation demonstrated the presence of two novel nuclear isoforms of ~110 and ~120kDa. Non-tumorigenic MCF10A breast epithelial cells stably transduced with shRNAs targeting giant obscurins exhibited increased viability (~30%) and reduced apoptosis (~20%) following exposure to the DNA damaging agent, etoposide. cDNA microarrays followed by Gene Ontology profiling indicated a substantial number of transcripts related to apoptosis and survival are differentially regulated upon obscurin knock-down. Quantitative RT-PCR further indicated that the anti-apoptotic genes BAG-4 and HAX-1 were up-regulated (1.5 and 1.4 fold, respectively), whereas initiator caspase-9 and death caspase-3 transcripts were down-regulated (0.8 and 0.6 fold, respectively). Our findings are the first to pinpoint critical roles for obscurins in cancer development by contributing to the regulation of cell survival.
Overall design Two-condition experiment: control shRNA- vs. obscurin shRNA-expressing MCF10A cells exposed to 150 uM etoposide. 3 independent replicates per condition.
Contributor(s) Perry NA, Shriver M, Mameza MG, Grabias B, Balzer E, Kontrogianni-Konstantopoulos A
Citation(s) 22441987
Submission date Feb 01, 2012
Last update date Feb 22, 2018
Contact name Aikaterini Kontrogianni-Konstantopoulos
Phone 410-706-5788
Fax 410-706-8297
Organization name University of Maryland, Baltimore
Street address 108 N Greene St
City Baltimore
ZIP/Postal code 21201
Country USA
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (3)
GSM869738 MCF10A cells expressing control or obscurin shRNA, exposed to etoposide 48 hr, replicate 1
GSM869739 MCF10A cells expressing control or obscurin shRNA, exposed to etoposide 48 hr, replicate 2
GSM869740 MCF10A cells expressing control or obscurin shRNA, exposed to etoposide 48 hr, replicate 3
BioProject PRJNA152291

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE35494_RAW.tar 26.0 Mb (http)(custom) TAR (of GPR)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap