Expression of MDR1 and GST-pi in human soft tissue sarcomas: relation to drug resistance and biological aggressiveness.
Human soft tissue sarcomas (HSTS) in adults are a family of mesenchymal tumors characterized by high biological aggressiveness and general refractoriness to chemotherapy. A series of 36 HSTS, 24 untreated and 12 homogeneously treated with a presurgical chemotherapeutic regimen consisting of doxorubicin (intra-arterial) and iphosphamide (intra-vein), was analyzed for expression of MDR1 and the glutathione-S-transferase-pi (GST-pi) gene in order to identify molecular phenomena which may be implicated in the chemoresistance displayed by these tumors. The MDR1 gene was expressed in a greater percentage of drug-treated tumors and at higher levels than in untreated ones. By contrast, chemotherapeutic treatment has no effect on GST-pi mRNA expression. The GST-pi expression level (EL) was much higher in the HSTS with biologically aggressive features. In fact, significant correlations were observed between GST-pi and histologic grade (p = 0.01); aneuploidy (p less than 0.01); and histone H3 EL (p = 0.01), suggesting a possible causal relationship between GST-pi activity and biological aggressiveness in HSTS.
Toffoli
G
G
Centro di Riferimento Oncologico, Aviano, Italy.
Frustaci
S
S
Tumiotto
L
L
Talamini
R
R
Gherlinzoni
F
F
Picci
P
P
Boiocchi
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004247:DNA / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006657:Histones / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D012509:Sarcoma / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000235:genetics*
D006657:Histones; D007527:Isoenzymes; D012333:RNA, Messenger; D004247:DNA; D005982:Glutathione Transferase