title: Expression of major vault protein gene in osteosarcoma patients.
abstract: Osteosarcoma (OS) is a primary malignant tumor of bone. Despite the successful use of multiple chemotherapeutic agents in the treatment of OS, more than 30% of OS tumors remain resistant to treatment. Elucidation of cellular resistance mechanisms may lead to better treatments for cancer patients. In this study, we used the low-density expression cDNA array, GEArray Q Series Human Cancer Drug Resistance and Metabolism Gene Array to screen genes related to drug resistance in 15 OS tumors. Expression patterns of the MPV gene were validated by real time PCR on 45 OS patient tumor samples and correlated with clinical and pathological data. Major vault protein (MVP) expression was present in 24 (53%) tumor samples and absent in 21 (47%). Samples from surgery showed correlation between the expression of MVP, metastatic disease at diagnosis and event free survival (EFS). The MVP gene expression correlates with metastatic disease at diagnosis after neoadjuvant chemotherapy (p=0.048), and is also associated with worse EFS (p=0.036). These findings suggest that MVP expression is involved in one of the mechanisms of drug resistance in OS and is induced by chemotherapy.
authors.affiliation: Department of Pediatrics, Instituto de Oncologia Pediátrica, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil, and Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: Cristiane Arruda
authors.initials: CA
authors.lastname: Dalla-Torre
authors.forename: Silvia Regina Caminada
authors.initials: SR
authors.lastname: de Toledo
authors.forename: Maisa
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Antônio Sérgio
authors.initials: AS
authors.lastname: Petrilli
authors.forename: Joyce Anderson Duffles
authors.initials: JA
authors.lastname: Andrade
authors.forename: Susan
authors.initials: S
authors.lastname: Chilton-MacNeill
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
authors.forename: Maria
authors.initials: M
authors.lastname: Zielenska
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D020360:Neoadjuvant Therapy; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics* / Q000378:metabolism; D000099187:Major Vault Protein
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein