ABC transporter gene expression in benign and malignant ovarian tissue.
OBJECTIVE
ATP-binding Cassette (ABC) transporters are thought to cause multiple drug resistance (MDR) in various carcinomas. Gene expression data from individual transporters in ovarian cancer tissue is contradictory and also scarce for some of them. RNA levels of a panel of ABC transporters were collected and analyzed to get a more detailed overview which transporters are of importance in resistance to chemotherapeutic agents in ovarian carcinoma.


METHODS
Real-time PCR was used to determine RNA expression levels of 9 ABC transporters in 50 benign tissue samples and 50 recurrent ovarian cancer samples. Genes exhibiting a significant difference between those two groups were further evaluated in 50 primary cancer samples. Data were analyzed with receiver operating characteristic (ROC) curves and multiple Wilcoxon-Mann-Whitney U-tests with Shaffer correction.


RESULTS
Gene expression of four transporters (ABCC1, ABCC2, ABCC3, and ABCB3) was significantly elevated in recurrent cancer lesions compared to benign tissue. Expression levels of these 4 ABC transporters were further analyzed in primary ovarian cancer lesions. A significant difference between primary and recurrent tumor tissue was found in all four genes. Changes in gene expression between benign samples and primary lesions were minor and not relevant.


CONCLUSIONS
Four of the examined ABC transporters are likely to play a role in the MDR of ovarian carcinoma. Gene expression of these transporters seems only up regulated through chemotherapy. The thesis that MDR in ovarian cancer is acquired through therapy itself and not present ab initio is supported by these findings.
Auner
Veronika
V
Division of Gynaecology, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria. veronika.auner@meduniwien.ac.at
Sehouli
Jalid
J
Oskay-Oezcelik
Gülten
G
Horvat
Reinhard
R
Speiser
Paul
P
Zeillinger
Robert
R
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003537:Cystadenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D015870:Gene Expression; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D012372:ROC Curve; D015854:Up-Regulation; D000093542:Gemcitabine
C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D003841:Deoxycytidine; D003520:Cyclophosphamide; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine