Expression of genes of potential importance in the response to chemotherapy and DNA repair in patients with ovarian cancer.
The expression of different genes potentially involved in DNA repair and in cell responses to chemotherapy was evaluated in 33 previously untreated ovarian cancer patients. In biopsies of the same patients the expression of repair genes O6-methylguanine DNA methyltransferase (MGMT), 3-methyladenine DNA glycosylase (MAG), ERCC1, MDR-1, DNA topoisomerase I, DNA topoisomerase IIalpha, and glutathione S-transferase-pi (GST-pi) was assessed by Northern blot analysis. No direct statistical correlation was found between the expression of these genes and the response to chemotherapy (mainly platinum-based with or without doxorubicin and cyclophosphamide). Univariate analysis showed a weak negative correlation (P = 0.037) between the expression of ERCC1 and mortality, whereas no statistically significant correlation was found for other parameters. The MDR-1 gene encoding for the P-glycoprotein P-170 was mostly undetectable in these patients (as assessed by Northern blotting), whereas relatively high levels of MAG and MGMT were found in the majority of patients. A statistically significant correlation was found between the expression of DNA topoisomerase I and the expression of either ERCC1 (P = 0.0026) or GST-pi (P = 0.0279).
Codegoni
A M
AM
Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Broggini
M
M
Pitelli
M R
MR
Pantarotto
M
M
Torri
V
V
Mangioni
C
C
D'Incalci
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015152:Blotting, Northern; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D045647:DNA Glycosylases; D004260:DNA Repair / Q000235:genetics*; D004264:DNA Topoisomerases, Type I / Q000032:analysis / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple; D004720:Endonucleases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005982:Glutathione Transferase / Q000032:analysis / Q000235:genetics; D006801:Humans; D008780:Methyltransferases / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000032:analysis / Q000235:genetics; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics*; D010053:Ovary / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D011506:Proteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005982:Glutathione Transferase; C071447:ERCC1 protein, human; D004720:Endonucleases; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D002945:Cisplatin