Expression of resistance-related proteins in nephroblastoma after chemotherapy

Int J Cancer. 1995 Oct 9;63(2):193-7. doi: 10.1002/ijc.2910630208.

Abstract

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Antineoplastic Agents / therapeutic use
  • Base Sequence
  • DNA Primers / chemistry
  • DNA Topoisomerases, Type II / genetics*
  • Dactinomycin / therapeutic use
  • Drug Resistance, Multiple
  • Gene Expression Regulation, Neoplastic
  • Glutathione Peroxidase / genetics*
  • Glutathione Transferase / genetics*
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Retrospective Studies
  • Vincristine / therapeutic use
  • Wilms Tumor / drug therapy
  • Wilms Tumor / genetics
  • Wilms Tumor / metabolism*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • DNA Primers
  • RNA, Messenger
  • RNA, Neoplasm
  • Dactinomycin
  • Vincristine
  • Glutathione Peroxidase
  • Glutathione Transferase
  • DNA Topoisomerases, Type II