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 genesO6-methylguanine DNA methyltransferase (MGMT), 3-methyladenine D...

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Bibliographic Details
Published in:	Gynecologic oncology Vol. 65; no. 1; pp. 130 - 137
Main Authors:	Codegoni, A.M., Broggini, M., Pitelli, M.R., Pantarotto, M., Torri, V., Mangioni, C., D'Incalci, M.
Format:	Journal Article
Language:	English
Published:	San Diego, CA Elsevier Inc 01-04-1997 Elsevier
Subjects:	Adult Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use ATP-Binding Cassette, Sub-Family B, Member 1 - analysis ATP-Binding Cassette, Sub-Family B, Member 1 - genetics Biological and medical sciences Blotting, Northern Carboplatin - administration & dosage Cisplatin - administration & dosage Cyclophosphamide - administration & dosage DNA Glycosylases DNA Repair - genetics DNA Topoisomerases, Type I - analysis DNA Topoisomerases, Type I - genetics DNA Topoisomerases, Type II - analysis DNA Topoisomerases, Type II - genetics DNA, Neoplasm - genetics DNA-Binding Proteins Doxorubicin - administration & dosage Drug Resistance, Multiple Endonucleases Female Female genital diseases Gene Expression Regulation, Neoplastic - drug effects Glutathione Transferase - analysis Glutathione Transferase - genetics Gynecology. Andrology. Obstetrics Humans Medical sciences Methyltransferases - analysis Methyltransferases - genetics Middle Aged N-Glycosyl Hydrolases - analysis N-Glycosyl Hydrolases - genetics O-Methylguanine-DNA Methyltransferase Ovarian Neoplasms - chemistry Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovary - chemistry Ovary - pathology Ovary - physiopathology Proteins - analysis Proteins - genetics RNA, Messenger - analysis RNA, Messenger - chemistry RNA, Messenger - genetics Tumors Antineoplastic agent Human Genetic inheritance Malignant tumor Female genital diseases Northern blotting Ovarian diseases Ovary Chemotherapy Gene DNA Cytopathology Female Molecular biology Mechanism of action Repair Negative therapeutic reaction
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Summary:	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 genesO6-methylguanine DNA methyltransferase (MGMT), 3-methyladenine DNA glycosylase (MAG), ERCC1, MDR-1, DNA topoisomerase I, DNA topoisomerase IIα, and glutathioneS-transferase-π (GST-π) 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-π (P= 0.0279).
ISSN:	0090-8258 1095-6859
DOI:	10.1006/gyno.1996.4609