Expression of major vault protein gene in osteosarcoma patients.
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.
Dalla-Torre
Cristiane Arruda
CA
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.
de Toledo
Silvia Regina Caminada
SR
Yoshimoto
Maisa
M
Petrilli
Antônio Sérgio
AS
Andrade
Joyce Anderson Duffles
JA
Chilton-MacNeill
Susan
S
Squire
Jeremy A
JA
Zielenska
Maria
M
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
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein