Identification of potential chemoresistance genes in osteosarcoma.
BACKGROUND
Osteosarcoma (OS) is an aggressive bone malignancy that primarily affects children and adolescents. Patients with metastatic disease at diagnosis have only a 20% survival rate. The poor survival rate of these patients is largely due to their lack of responsiveness to chemotherapy. However, the mechanisms underlying osteosarcoma chemoresistance remain unknown.


METHODS
The effect of cisplatin, doxorubicin and etoposide was examined on OS cell lines. Affymetric Genechip analysis was used to examine differential gene expression.


RESULTS
A correlation between increasing metastatic potential and increasing chemoresistance was observed in the MG-63 cell line and sub-line model. Microarray analysis of these cell lines revealed the differential expression of several genes potentially involved in chemoresistance including ABCG2, ADD3, NMT2, WNTSa and PTN.


CONCLUSIONS
The identification of genes contributing to chemoresistance and determining the role these genes play is critical in characterizing patient responsiveness and overcoming chemoresistance in osteosarcoma patients.
Walters
Denise Katherine
DK
Laboratory for Orthopaedic Research, Department of Orthopaedics, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Steinmann
Patrick
P
Langsam
Bettina
B
Schmutz
Silvia
S
Born
Walter
W
Fuchs
Bruno
B
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000235:genetics*
D000970:Antineoplastic Agents