title: Gene expression changes associated with erlotinib response in glioma cell lines.
abstract: Erlotinib (ERL), a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor (EGFR), is used as a second line treatment for glioma therapy, with controversial findings regarding its response. Here, we analysed the gene expression profiles of a series of human glioma cell lines with differing sensitivities to ERL to identify the gene expression changes associated with ERL response. The varying responses to ERL were associated with different expression levels of specific genes (HRAS, CTFG, ERCC5 and HDAC3) and genes associated with specific pathways (apoptosis and cell death). PI3K pathway genes were primarily affected by ERL, as we found that PIK3R3 was repressed by ERL treatment in sensitive glioma cell lines. The cell cycle and ubiquitin pathways were also affected by EGFR inhibition, as GAS5, PLK1 and BIRC5 were the most significantly affected genes. In this study we have identified several genes such as PIK3R3 and GAS5, that can be targeted in order to enhance the response to ERL therapy.
authors: Molecular Pathology Research Unit, Virgen de la Salud Hospital, Toledo, Spain.
authors: Ainoha
authors: A
authors: García-Claver
authors: Mar
authors: M
authors: Lorente
authors: Pilar
authors: P
authors: Mur
authors: Yolanda
authors: Y
authors: Campos-Martín
authors: Manuela
authors: M
authors: Mollejo
authors: Guillermo
authors: G
authors: Velasco
authors: Bárbara
authors: B
authors: Meléndez
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016000:Cluster Analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000235:genetics / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D011799:Quinazolines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D014157:Transcription Factors / Q000235:genetics; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D004720:Endonucleases; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D051034:Inhibitor of Apoptosis Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines; D000077022:Survivin; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C107489:BIRC5 protein, human; C512478:EGFR protein, human; C501009:HRAS protein, human