Transcriptome profile of OVCAR3 cisplatin-resistant ovarian cancer cell line
© Sakhare et al; licensee BioMed Central Ltd. 2014
Published: 29 September 2014
The NIH:OVCAR-3 is a cisplatin refractory cell line established from malignant ascites of a patient with progressive adenocarcinoma of the ovary after combination chemotherapy with cyclophosphamide, Adriamycin, and cisplatin . Thus, OVCAR3 serves as a model cell line for drug resistance in ovarian cancer. Here, we perform a comparative transcriptome analysis from the US National Cancer Institute human tumor cell line anticancer drug screen (NCI60) dataset . Our results indicate a specific gene transcription profile of OVCAR3 genes relative to non-cancerous Human Ovarian Surface Epithelial cells (HOSE) and drug sensitive Serous Ovarian Cancer Epithelial Samples (CEPI) and SKOV3 cell lines. Pathway enrichment analysis from OVCAR3 unique transcripts was conducted using KEGG; Disease and Drug term enrichment used the PharmGKB  databases.
Materials and methods
Datasets from the NCI60 were obtained from the Gene Expression Omnibus (GEO) of NCBI  (OVCAR3 and SKOV3 from series GSE2003, OSE and CEPI from series GDS3592 and GSE14407). Transcriptome data analysis was conducted with Partek Genomics Suite version 6.6. The WEB-based GEne SeT AnaLysis Toolkit (WebGestalt) was used to perform enrichment analysis . Genes present in KEGG pathway, PharmGKB Disease, and Drug terms enrichment sets were connected and expanded to one degree of biological interaction using the Michigan Molecular Interactions databases plugin  and visualized using Cytoscape version 2.8.3 .
Transcripts differentially expressed in OVCAR3 versus SKOV3 and CEPI having significant enrichment scores in KEGG Pathway, PharmGKB Drug and Disease databases.
ATP-binding cassette, sub-family C (CFTR/MRP), member 4
aldo-keto reductase family 1, member C2 (dihydrodiol dehydrogenase 2; bile acid binding protein; 3-alpha hydroxysteroid dehydrogenase, type III)
mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)
integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)
UDP glucuronosyltransferase 1 family, polypeptide A6
peroxisome proliferator-activated receptor gamma
prostaglandin I2 (prostacyclin) synthase
ATP-binding cassette, sub-family C (CFTR/MRP), member 3
UDP glucuronosyltransferase 1 family, polypeptide A1
v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)
aldo-keto reductase family 1, member C1 (dihydrodiol dehydrogenase 1; 20-alpha (3-alpha)-hydroxysteroid dehydrogenase)
fibroblast growth factor 2 (basic)
Funding provided by NIH grants MD007586 and MD007593 from the National Institute on Minority Health and Health Disparities (NIMHD).
- Hamilton TC, Young RC, McKoy WM, Grotzinger KR, Green JA, Chu EW, Whang-Peng J, Rogan AM, Green WR, Ozols RF: Characterization of a human ovarian carcinoma cell line (NIH: OVCAR-3) with androgen and estrogen receptors. Cancer Res. 1983, 43 (11): 5379-5389.PubMedGoogle Scholar
- Shoemaker RH: The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer. 2006, 6 (10): 813-823. 10.1038/nrc1951.View ArticlePubMedGoogle Scholar
- Whirl-Carrillo M, McDonagh E, Hebert J, Gong L, Sangkuhl K, Thorn C, Altman R, Klein TE: Pharmacogenomics knowledge for personalized medicine. Clin PharmTher. 2012, 92 (4): 414-417.Google Scholar
- Gene Expression Omnibus. [http://www.ncbi.nlm.nih.gov/geo/]
- Wang J, Duncan D, Shi Z, Zhang B: WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 2013, 41 (W1): W77-W83. 10.1093/nar/gkt439.PubMed CentralView ArticlePubMedGoogle Scholar
- Tarcea VG, Weymouth T, Ade A, Bookvich A, Gao J, Mahavisno V, Wright Z, Chapman A, Jayapandian M, Özgür A: Michigan molecular interactions r2: from interacting proteins to pathways. Nucleic Acids Res. 2009, 37 (suppl 1): D642-D646.PubMed CentralView ArticlePubMedGoogle Scholar
- Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003, 13 (11): 2498-2504. 10.1101/gr.1239303.PubMed CentralView ArticlePubMedGoogle Scholar
- Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H, Schiff R: Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2–positive breast cancer. J Nat Cancer Inst. 2004, 96 (12): 926-935. 10.1093/jnci/djh166.View ArticlePubMedGoogle Scholar
- Lu KV, Zhu S, Cvrljevic A, Huang TT, Sarkaria S, Ahkavan D, Dang J, Dinca EB, Plaisier SB, Oderberg I: Fyn and SRC are effectors of oncogenic epidermal growth factor receptor signaling in glioblastoma patients. Cancer Res. 2009, 69 (17): 6889-6898. 10.1158/0008-5472.CAN-09-0347.PubMed CentralView ArticlePubMedGoogle Scholar
- Palomero T, Couronné L, Khiabanian H, Kim M-Y, Ambesi-Impiombato A, Perez-Garcia A, Carpenter Z, Abate F, Allegretta M, Haydu JE: Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014, 46 (2): 166-170. 10.1038/ng.2873.PubMed CentralView ArticlePubMedGoogle Scholar
- Le X-F, Mao W, He G, Claret F-X, Xia W, Ahmed AA, Hung M-C, Siddik ZH, Bast RC: The role of p27Kip1 in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. J Nat Cancer Inst. 2011, 103 (18): 1403-1422. 10.1093/jnci/djr280.PubMed CentralView ArticlePubMedGoogle Scholar
- Vaughan S, Coward JI, Bast RC, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D: Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011, 11 (10): 719-725. 10.1038/nrc3144.PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.