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Series GSE36847 Query DataSets for GSE36847
Status Public on May 21, 2012
Title Distinct perturbation of the translatome by the anti-diabetic drug metformin
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Reduced cancer incidence has been reported among type II diabetics treated with metformin. Metformin exhibits anti-proliferative and anti-neoplastic effects associated with inhibition of mTORC1, but the mechanisms are poorly understood. We provide the first genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) and metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's anti-proliferative activity can be explained by selective translational suppression of mRNAs encoding cell cycle regulators via the mTORC1/4E-BP pathway. Thus, metformin selectively inhibits mRNA translation of encoded proteins that promote neoplastic proliferation, motivating further studies of this compound and related biguanides in cancer prevention and treatment.
 
Overall design MCF7 cells were treated with rapamycin, metformin or PP242 at concentrations that inhibited proliferation to 50% of control. Both cytoplasmic and polysome-associated mRNA was extracted from treatments and a vehicle treated control and probed with microarrays.
 
Contributor(s) Larsson O, Sonenberg N
Citation(s) 22611195
Submission date Mar 27, 2012
Last update date Jun 25, 2012
Contact name Ola Larsson
E-mail(s) ola.larsson@ki.se
Phone +46 (0)8 517 73280
Organization name Karolinska Institutet
Department Department of oncology-pathology
Street address CCK, R8:01
City Stockholm
ZIP/Postal code 171 76
Country Sweden
 
Platforms (1)
GPL14877 Affymetrix Human Genome U133 Plus 2.0 Array [Brainarray Version 13, HGU133Plus2_Hs_ENTREZG]
Samples (32)
GSM902879 metformin 12h treatment, replicate 1 polysome-associated RNA
GSM902880 metformin 12h treatment, replicate 1 cytosolic RNA
GSM902881 rapamycin 12h treatment, replicate 1 polysome-associated RNA
Relations
BioProject PRJNA156903

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE36847_RAW.tar 165.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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