| Literature DB >> 28251557 |
Pang-Ning Teng1, Nicholas W Bateman1,2,3, Guisong Wang1, Tracy Litzi1, Brian E Blanton1, Brian L Hood1, Kelly A Conrads1, Wei Ao1, Kate E Oliver4, Kathleen M Darcy1,2, William P McGuire5, Keren Paz6, David Sidransky7, Chad A Hamilton1,2,4, G Larry Maxwell1,2,8,9, Thomas P Conrads10,11,12,13,14.
Abstract
High grade serous ovarian cancer (HGSOC) patients have a high recurrence rate after surgery and adjuvant chemotherapy due to inherent or acquired drug resistance. Cell lines derived from HGSOC tumors that are resistant to chemotherapeutic agents represent useful pre-clinical models for drug discovery. Here, we describe establishment of a human ovarian carcinoma cell line, which we term WHIRC01, from a patient-derived mouse xenograft established from a chemorefractory HGSOC patient who did not respond to carboplatin and paclitaxel therapy. This newly derived cell line is platinum- and paclitaxel-resistant with cisplatin, carboplatin, and paclitaxel half-maximal lethal doses of 15, 130, and 20 µM, respectively. Molecular characterization of this cell line was performed using targeted DNA exome sequencing, transcriptomics (RNA-seq), and mass spectrometry-based proteomic analyses. Results from exomic sequencing revealed mutations in TP53 consistent with HGSOC. Transcriptomic and proteomic analyses of WHIRC01 showed high level of alpha-enolase and vimentin, which are associated with cell migration and epithelial-mesenchymal transition. WHIRC01 represents a chemorefractory human HGSOC cell line model with a comprehensive molecular profile to aid future investigations of drug resistance mechanisms and screening of chemotherapeutic agents.Entities:
Keywords: Cell line; High grade serous; Ovarian cancer; Paclitaxel resistance; Platinum resistance
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Year: 2017 PMID: 28251557 DOI: 10.1007/s13577-017-0162-1
Source DB: PubMed Journal: Hum Cell ISSN: 0914-7470 Impact factor: 4.174