Altered expression of resistance associated genes in hepatoblastoma xenografts incorporated into mice following treatment with adriamycin or cisplatin.
To study the development of drug resistance in childhood hepatoblastoma (HB) using a model closely related to in vivo conditions, we cultivated HB xenografts from 3 patients into mice and treated these tumors with either adriamycin (ADR) or cisplatin (CIS). Determination of the relative expression levels of various resistance associated genes by a cDNA-PCR approach showed: a) Significantly enhanced MDR1 gene expression levels after treatment with ADR in each case. b) Significantly enhanced glutathione S-transferase mu (GST mu) gene expression levels after treatment with CIS in 2/3 xenografts. c) Significantly decreased levels of topoisomerase IIa (TOPO IIa) in tumors of the same two patients after treatment with either ADR or CIS. These findings give evidence that the MDR1-, GST mu- and TOPO IIa-gene products may contribute to drug resistance in HB.
University Children's Hospital, Department Hematology and Oncology, Tübingen, Germany.
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P
Bader
J
J
Fuchs
M
M
Wenderoth
D
D
von Schweinitz
D
D
Niethammer
J F
JF
Beck
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D019925:Cyclin A / Q000096:biosynthesis / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000903:Antibiotics, Antineoplastic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002945:Cisplatin; D019925:Cyclin A; D004250:DNA Topoisomerases, Type II; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D005982:Glutathione Transferase; D007069:Ifosfamide; D007527:Isoenzymes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein