Microarray-based detection and expression analysis of new genes associated with drug resistance in ovarian cancer cell lines
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Radosław Januchowski1, Karolina Sterzyńska1, Piotr Zawierucha1,2, Marcin Ruciński1, Monika Świerczewska1, Małgorzata Partyka1, Katarzyna Bednarek-Rajewska3, Maciej Brązert4, Michał Nowicki1, Maciej Zabel1,5 and Andrzej Klejewski6,7
1Department of Histology and Embryology, Poznań University of Medical Sciences, Poznań, 60-781, Poland
2Department of Anatomy, Poznań University of Medical Sciences, Poznań, 60-781, Poland
3Department of Clinical Pathomorphology, Poznań University of Medical Sciences, Poznań, 60-355, Poland
4Division of Infertility and Reproductive Endocrinology, Department of Gynecology, Obstetrics and Gynecological Oncology, Poznań University of Medical Sciences, Poznań, 60-535, Poland
5Department of Histology and Embryology, Wrocław Medical University, Wrocław, 50-368, Poland
6Department of Nursing, Poznań University of Medical Sciences, Poznań, 60-179, Poland
7Department of Obstetrics and Womens Dieseases, Poznań University of Medical Sciences, Poznań, 60-535, Poland
Radosław Januchowski, email: firstname.lastname@example.org
Keywords: ovarian cancer, drug resistance, cDNA microarray, new genes
Received: March 08, 2017 Accepted: April 24, 2017 Published: May 29, 2017
Purpose: The present study is to discover a new genes associated with drug resistance development in ovarian cancer.
Methods: We used microarray analysis to determine alterations in the level of expression of genes in cisplatin- (CisPt), doxorubicin- (Dox), topotecan- (Top), and paclitaxel- (Pac) resistant variants of W1 and A2780 ovarian cancer cell lines. Immunohistochemistry assay was used to determine protein expression in ovarian cancer patients.
Results: We observed alterations in the expression of 22 genes that were common to all three cell lines that were resistant to the same cytostatic drug. The level of expression of 13 genes was upregulated and that of nine genes was downregulated. In the CisPt-resistant cell line, we observed downregulated expression of ABCC6, BST2, ERAP2 and MCTP1; in the Pac-resistant cell line, we observe upregulated expression of ABCB1, EPHA7 and RUNDC3B and downregulated expression of LIPG, MCTP1, NSBP1, PCDH9, PTPRK and SEMA3A. The expression levels of three genes, ABCB1, ABCB4 and IFI16, were upregulated in the Dox-resistant cell lines. In the Top-resistant cell lines, we observed increased expression levels of ABCG2, HERC5, IFIH1, MYOT, S100A3, SAMD4A, SPP1 and TGFBI and decreased expression levels of MCTP1 and PTPRK. The expression of EPHA7, IFI16, SPP1 and TGFBI was confirmed at protein level in analyzed ovarian cancer patients..
Conclusions: The expression profiles of the investigated cell lines indicated that new candidate genes are related to the development of resistance to the cytostatic drugs that are used in first- and second-line chemotherapy of ovarian cancer.
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