title: Proteomics identified overexpression of SET oncogene product and possible therapeutic utility of protein phosphatase 2A in alveolar soft part sarcoma.
abstract: Alveolar soft part sarcoma (ASPS) is an exceedingly rare sarcoma refractory to standard chemotherapy. Although several molecular targeting drugs have been applied for ASPS, their clinical significance has not yet been established, and novel therapeutic strategies have long been required. The aim of this study was to identify proteins aberrantly regulated in ASPS and to clarify their clinical significance. Protein expression profiling of tumor and nontumor tissues from 12 ASPS patients was performed by 2-D difference gel electrophoresis and mass spectrometry. We found that the expression of 145 proteins differed significantly. Among them, further investigation was focused on the SET protein, which has multifunctional roles in cancers. Immunohistochemistry confirmed overexpression of SET in all 15 ASPS cases examined. Gene silencing of SET significantly decreased cell proliferation, invasion, and migration against a background of induced apoptosis. SET is known to be an inhibitor of phosphatase 2A (PP2A), which functions as a tumor suppressor by inhibiting the signal transduction pathway and inducing apoptosis. We found that a PP2A activator, FTY720, decreased cell proliferation through apoptosis. Together, our findings may suggest the possible contribution of SET to the tumor progression and the utility of FTY720 for treatment of ASPS.
authors.affiliation: Division of Pharmacoproteomics, National Cancer Center Research Institute , Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kubota
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Akira
authors.initials: A
authors.lastname: Kawai
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D000068876:Fingolimod Hydrochloride; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D011409:Propylene Glycols / Q000494:pharmacology; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D034622:RNA Interference; D018234:Sarcoma, Alveolar Soft Part / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D020536:Enzyme Activators; D056488:Histone Chaperones; D009363:Neoplasm Proteins; D011409:Propylene Glycols; D020543:Proteome; C513473:SET protein, human; D014157:Transcription Factors; D054648:Protein Phosphatase 2; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine