scholarly journals Genomic Characterization of Cisplatin Response Uncovers Priming of Cisplatin-Induced Genes in a Resistant Cell Line

2021 ◽  
Vol 22 (11) ◽  
pp. 5814
Author(s):  
Hadar Golan Berman ◽  
Pooja Chauhan ◽  
Shira Shalev ◽  
Hiba Hassanain ◽  
Avital Parnas ◽  
...  
Keyword(s):  
Cell Line ◽  
Nucleotide Excision Repair ◽  
Cisplatin Resistance ◽  
Excision Repair ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Nucleotide Excision ◽  
Genomic Characterization ◽  
Resistant Cells

Cisplatin is a chemotherapy drug that kills cancer cells by damaging their DNA. In human cells, this damage is repaired primarily by nucleotide excision repair. While cisplatin is generally effective, many cancers exhibit initial or acquired resistance to it. Here, we studied cisplatin resistance in a defined cell line system. We conducted a comprehensive genomic characterization of the cisplatin-sensitive A2780 ovarian cancer cell line compared to A2780cis, its resistant derivative. The resistant cells acquired less damage, but had similar repair kinetics. Genome-wide mapping of nucleotide excision repair showed a shift in the resistant cells from global genome towards transcription-coupled repair. By mapping gene expression changes following cisplatin treatment, we identified 56 upregulated genes that have higher basal expression in the resistant cell line, suggesting they are primed for a cisplatin response. More than half of these genes are novel to cisplatin- or damage-response. Six out of seven primed genes tested were upregulated in response to cisplatin in additional cell lines, making them attractive candidates for future investigation. These novel candidates for cisplatin resistance could prove to be important prognostic markers or targets for tailored combined therapy in the future.

Abstract B14: Characterization of p53-HDM2 inhibitor in nucleotide excision repair deficient cell line

2018 ◽  
Author(s):  
Douglas Felipe de Lima Silva ◽  
Ana Rafaela de Souza Timoteo ◽  
Lucymara Fassarela Agnez Lima ◽  
Tirzah Braz Petta Lajus
Keyword(s):  
Cell Line ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Deficient Cell ◽  
Nucleotide Excision

Isolation and characterization of NaCl resistant cell line of mulberry

1995 ◽  
Vol 37 (3) ◽  
Author(s):  
K. Kathiravan ◽  
A. Shajahan ◽  
A. Ganapathi
Keyword(s):  
Cell Line ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Isolation And Characterization

scholarly journals Generating Paclitaxel-Resistant in Cervical Cancer HeLa Cell Line

2020 ◽  
Vol 11 (2) ◽  
pp. 90
Author(s):  
Muhammad Hasan Bashari ◽  
Fachreza Aryo Damara ◽  
Isna Nisrina Hardani ◽  
Gita Widya Pradini ◽  
Tenny Putri ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Line ◽  
Hela Cells ◽  
Molecular Mechanisms ◽  
Inhibitory Concentration ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Resistant Cells

Cervical cancer is one of the most leading causes of women death. Currently, paclitaxel is still one of the main therapeutic regimens for cervical cancer patients. However, some patients developed to be paclitaxel-resistant. Hence, studies to find out the novel strategies to resolve this problem are important. Generating resistant cancer cell lines can be utilized as the potent tool to evaluate the efficacy of any therapeutic agent toward cancer drug-resistant problems. Current studies describing the methods to establish chemoresistance are lacking. Moreover, study in Indonesia conducting chemoresistance in cell line is limited. This study was aimed to elaborate the characteristics of HeLa cells during generation of paclitaxel-resistant cervical cancer cells. The parental HeLa cells were exposed to an escalating concentration of paclitaxel for a long time period. Subsequently, cells were divided into two groups for the evaluation of resistance characteristics. The values of inhibitory concentration 50 (IC50) and inhibitory concentration 90 (IC90) were analyzed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Our data showed that the longer exposing periods of paclitaxel, the higher IC50 and IC90 values of HeLa cells are. IC90 of paclitaxel in HeLa Pac RB was increased from 69 pM, 440 pM, 2,561 pM and 10,337 pM on 0th, 1st, 2nd, 3rd and 4th months, respectively. Interestingly, the resistant cells were recovered to be paclitaxel-sensitive when they were not being continuously exposed to paclitaxel. In addition, the paclitaxel resistant cells become less sensitive against 5-FU but not doxorubicin, cisplatin and etoposide. We were able to generate cervical cancer HeLa paclitaxel-resistant cell line. These cell line could potentially be utilized for further studies in order to understand the molecular mechanisms of drug resistance in cervical cancer and as a tool for cancer drug discovery.Keywords: cervical cancer, drug resistant cell line, paclitaxel resistant cells, stepwise escalating concentration.

Molecular cloning and biological characterization of a human gene, ERCC2, that corrects the nucleotide excision repair defect in CHO UV5 cells

1988 ◽  
Vol 8 (3) ◽  
pp. 1137-1146
Author(s):  
C A Weber ◽  
E P Salazar ◽  
S A Stewart ◽  
L H Thompson
Keyword(s):  
Cell Line ◽  
Nucleotide Excision Repair ◽  
Human Gene ◽  
Excision Repair ◽  
Hybrid Cell ◽  
Repetitive Sequences ◽  
Chinese Hamster ◽  
Wild Type ◽  
Wild Type Level ◽  
Nucleotide Excision

The UV-sensitive Chinese hamster ovary (CHO) cell line UV5, which is defective in the incision step of nucleotide excision repair, was used to identify and clone a complementing human gene, ERCC2, and to study the repair process. Genomic DNA from a human-hamster hybrid cell line was sheared and cotransferred with pSV2gpt plasmid DNA into UV5 cells to obtain five primary transformants. Transfer of sheared DNA from one primary transformant resulted in a secondary transformant expressing both gpt and ERCC2. The human repair gene was identified with a probe for Alu-family repetitive sequences. For most primary, secondary, and cosmid transformants, survival after UV exposure showed a return to wild-type levels of resistance. The levels of UV-induced mutation at the aprt locus for secondary and cosmid transformants varied from 50 to 130% of the wild-type level. Measurements of the initial rate of UV-induced strand incision by alkaline elution indicated that, whereas the UV5 rate was 3% of the wild-type level, rates of cosmid-transformed lines were similar to that of the wild type, and the secondary transformant rate was about 165% of the wild-type rate. Analysis of overlapping cosmids determined that ERCC2 is between 15.5 and 20 kilobases and identified a closely linked gpt gene. Cosmids were obtained with functional copies of both ERCC2 and gpt. ERCC2 corrects only the first of the five CHO complementation groups of incision-defective mutants.

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