title: Proteomics and bioinformatics analysis of lovastatin-induced differentiation in ARO cells.
abstract: Lovastatin (lova), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, can induce differentiation in cancer cells at low concentration, thus having potential to be used as an auxiliary agent in cancer therapy. However, biological networks associated with the differentiation effect of lova have not been elucidated. To investigate molecular mechanisms of lova, the present study was aimed at proteomics and bioinformatics analyses on anaplastic thyroid cancer cell line ARO differentiated with low concentration of lova. Thyroid differentiation was induced by treating ARO cells with 25 μM of lova and confirmed by checking upregulation of some thyroid differentiation markers. Gel-based proteomics analysis was then performed to identify proteins differentially expressed between undifferentiated and lova-differentiated ARO cells. Bioinformatics analysis was finally performed to estimate biological networks regulated by lova. Our results showed that lova impacted on proteins involved in protein folding, biomolecule metabolism, signal transduction, protein expression and protein degradation. Specifically, transfecting ARO cells with plasmid DNA encoding flotillin 1 (FLOT1) up-regulated the thyroid differentiation markers, indicating that FLOT1 might at least partially mediate the lova-induced thyroid differentiation. These data may shed light on the mechanism underlying lova-induced re-differentiation of thyroid cancer, and give a rationale for clinical use of lova as an auxiliary agent in cancer therapy.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hao-Ai
authors.initials: HA
authors.lastname: Shui
authors.forename: Ching-Wu
authors.initials: CW
authors.lastname: Hsia
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Chen
authors.forename: Tien-Chun
authors.initials: TC
authors.lastname: Chang
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods*; D053938:DNA Fragmentation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology*; D008565:Membrane Proteins / Q000096:biosynthesis; D017510:Protein Folding; D040901:Proteomics / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008565:Membrane Proteins; C106354:flotillins; D008148:Lovastatin