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Gene expression of DNA topoisomerases I, IIα and IIβ and response to cisplatin‐based chemotherapy in advanced ovarian carcinoma
Author(s) -
Cornarotti Mariagrazia,
Capranico Giovanni,
Bohm Silvia,
Oriana Saro,
Spatti Gian Battista,
Mariani Luigi,
Ballabio Giuseppina,
Zunino Franco
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960807)67:4<479::aid-ijc3>3.0.co;2-p
Subject(s) - topoisomerase , cisplatin , ovarian cancer , ovarian carcinoma , chemotherapy , biology , cancer research , gene expression , dna damage , carcinoma , cancer , microbiology and biotechnology , gene , pathology , dna , medicine , genetics
DNA topoisomerases, nuclear enzymes that regulate DNA topology, are recognized as the primary targets of effective anti‐tumor drugs. These enzymes may also have a role in the repair of DNA damage induced by alkylating agents and platinum compounds; therefore, their expression may be a determinant of tumor response to chemotherapy. Our study was undertaken in an attempt to establish a correlation between the enzyme expression and response of ovarian cancer to cisplatin‐based chemotherapy. The expression of topoisomerase I, IIα and IIβ genes was assessed by RNase protection assay in tumor specimens obtained from 37 untreated patients with advanced epithelial ovarian cancer at initial surgery and from 13 pre‐treated patients at subsequent laparotomy. The expression levels were compared with those found in 5 specimens from benign ovarian tissue and 5 specimens from normal ovarian tissue. The expression levels in untreated patients were used to establish a correlation with response to high‐dose cisplatin therapy. A significant intertumor variability of mRNA expression was noted for all the genes examined. However, a comparison of median values indicated a remarkable increase of expression in malignant tumors over benign or normal tissues only for topoisomerase IIα. This change is not related to alterations or amplification of topoisomerase IIα gene. Interestingly, a correlation was found between tumor response to chemotherapy and the expression level of the isoform α (but not of topoisomerase IIβ and topoisomerase I). The observed correlation suggests a contribution of the enzyme in determining tumor sensitivity. Alternatively, increased expression levels of the α isoenzyme gene in responsive tumors might reflect higher fractions of proliferating tumor cells that may be more drug‐sensitive than resting cells. © 1996 Wiley‐Liss, Inc.