Investigation Title Transcription profiling of doxorubicin sensitive and resistant human myeloma cell lines after treatment with doxorubicin to explore the role of the STAT1 signaling pathway in drug and radiation resistance Comment[Submitted Name] 050928_8226S_DOX Experimental Design compound_treatment_design co-expression_design in_vitro_design transcription profiling by array Experimental Design Term Source REF mo mo EFO Comment[ArrayExpressReleaseDate] 2007-01-10 Comment[AEMIAMESCORE] 4 Comment[ArrayExpressAccession] E-BASE-2 Comment[MAGETAB TimeStamp_Version] 2011-06-28 11:31:43 Last Changed Rev: 14857 Experimental Factor Name compound phenotype Experimental Factor Type compound_treatment_design phenotype Experimental Factor Term Source REF Person Last Name Goransson Person First Name Hanna Person Mid Initials Person Email Hanna.Goransson@genpat.uu.se Person Phone Person Fax Person Address University of Uppsala, Uppsala, Sweden Person Affiliation University of Uppsala, Uppsala, Sweden Person Roles submitter Person Roles Term Source REF Quality Control Type dye_swap_design:replicate_design Quality Control Term Source REF Replicate Type Replicate Term Source REF Normalization Type Normalization Term Source REF Date of Experiment Public Release Date 2007-01-10 PubMed ID Publication DOI Publication Author List Fryknas M, Dhar S, Oberg F, Rickardson L, Rydaker M, Goransson H, Gustafsson M, Pettersson U, Nygren P, Larsson R, Isaksson A Publication Title STAT1 signaling is associated with acquired crossresistance to doxorubicin and radiation in myeloma cell lines. Publication Status Publication Status Term Source REF Experiment Description The myeloma cell line RPMI 8226/S and its doxorubicin resistant subline 8226/Dox40 were used as models to explore the potential importance of the STAT1 signaling pathway in drug and radiation resistance. The 40-fold doxorubicin resistant subline 8226/Dox40 was found to be crossresistant to single doses of 4 and 8 Gy of radiation. A genome-wide mRNA expression study comparing the 8226/Dox40 cell line to its parental line was performed to identify the underlying molecular mechanisms. Seventeen of the top 50 overexpressed genes have previously been implicated in the STAT1 signaling pathway. STAT1 was over expressed both at the mRNA and protein level. Moreover, analyses of nuclear extracts showed higher abundance of phosphorylated STAT1 (Tyr 701) in the resistant subline. Preexposure of the crossresistant cells to the STAT1 inhibiting drug fludarabine reduced expression of overexpressed genes and enhanced the effects of both doxorubicin and radiation. These results show that resistance to doxorubicin and radiation is associated with increased STAT1 signaling and can be modulated by fludarabine. The data support further development of therapies combining fludarabine and radiation. Protocol Name P-BASE-Trizol P-TABM-946 P-TABM-945 P-TABM-944 Protocol Type labeling hybridization feature_extraction Protocol Description Trizol Genisphere labelling protocol Genesphere hybridization protocol Genepix pro scanning protocol Protocol Parameters Protocol Hardware Protocol Software Protocol Contact Protocol Term Source REF mo SDRF File E-BASE-2.sdrf.txt Term Source Name ncbitax nci_meta The MGED Ontology ArrayExpress mo EFO Term Source File http://www.ncbi.nlm.nih.gov/Taxonomy/taxonomyhome.html http://ncimeta.nci.nih.gov/indexMetaphrase.html http://mged.sourceforge.net/ontologies/MGEDontology.php http://www.ebi.ac.uk/arrayexpress http://mged.sourceforge.net/ontologies/MGEDontology.php http://www.ebi.ac.uk/efo/ Term Source Version