Expression of resistance-related proteins in nephroblastoma after chemotherapy.
Tumor tissues of untreated and cytostatic-agent-treated patients with nephroblastomas were investigated for expression of resistance-related proteins (P-glycoprotein, glutathione S-transferase-pi, glutathione peroxidase and topoisomerase II) to ascertain whether resistance proteins are changed after treatment. Tumor tissue was analyzed by means of mRNA. Twenty-three children were treated with actinomycin D and vincristine for 4 to 8 weeks. Eight children received no preoperative chemotherapy. In untreated patients, no expression of P-glycoprotein was seen, whereas, in the patients who were treated with actinomycin D and vincristine, 12 out of 23 tumors showed increased P-glycoprotein expression (> mean value). Although we found no difference between treated and untreated tumors for glutathione S-transferase-pi, we found significant differences in the expression of glutathione peroxidase. In the 8 untreated patients, 7 tumors showed low glutathione peroxidase (< mean value) and one high (> mean value) glutathione-peroxidase-mRNA content. With treatment, 11 tumors expressed low levels and 12 tumors high levels of mRNA. A significant positive correlation between P-glycoprotein and glutathione peroxidase was found. In addition, of the 8 untreated patients, 2 had low topoisomerase-II expression, and 6 high expression. With treatment, the expression was reduced in 18 tumors, and only 5 tumors had high levels of this protein. These results were confirmed by PCR and immunohistochemistry.
Volm
M
M
German Cancer Research Center, Heidelberg, Germany.
Mattern
J
J
Stammler
G
G
Royer-Pokora
B
B
Schneider
S
S
Weirich
A
A
Ludwig
R
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D003609:Dactinomycin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012189:Retrospective Studies; D014750:Vincristine / Q000627:therapeutic use; D009396:Wilms Tumor / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003609:Dactinomycin; D014750:Vincristine; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II