scholarly journals PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations

2019 ◽  
Vol 20 (8) ◽  
pp. 2053 ◽  
Author(s):  
Świerczewska ◽  
Sterzyńska ◽  
Wojtowicz ◽  
Kaźmierczak ◽  
Iżycki ◽  
...  

Background: Ovarian cancer is the 7th most common cancer and 8th most mortal canceramong woman. The standard treatment includes cytoreduction surgery followed bychemotherapy. Unfortunately, in most cases, after treatment, cancer develops drug resistance.Decreased expression and/or activity of protein phosphatases leads to increased signaltransduction and development of drug resistance in cancer cells. Methods: Using sensitive (W1,A2780) and resistant ovarian cancer cell lines, the expression of Protein Tyrosine PhosphataseReceptor Type K (PTPRK) was performed at the mRNA (real‐time PCR analysis) and protein level(Western blot, immunofluorescence analysis). The protein expression in ovarian cancer tissues wasdetermined by immunohistochemistry. Results: The results showed a decreased level of PTPRKexpression in ovarian cancer cell lines resistant to cisplatin (CIS), paclitaxel (PAC), doxorubicin(DOX), topotecan (TOP), vincristine (VIN) and methotrexate (MTX). Additionally, the lowerPTPRK expression was observed in Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1)positive cancer stem cells (CSCs) population, suggesting the role of PTPRK downregulation inprimary as well as acquired resistance to cytotoxic drugs. Conclusions: These results provideimportant insights into the role of PTPRK in mechanism leading to drug resistance in ovariancancer and has raised important questions about the role of imbalance in processes ofphosphorylation and dephosphorylation.

Oncotarget ◽  
2017 ◽  
Vol 8 (30) ◽  
pp. 49944-49958 ◽  
Author(s):  
Radosław Januchowski ◽  
Karolina Sterzyńska ◽  
Piotr Zawierucha ◽  
Marcin Ruciński ◽  
Monika Świerczewska ◽  
...  

2010 ◽  
Vol 4 (S2) ◽  
Author(s):  
Fernanda Silva ◽  
Jacinta Serpa ◽  
Germana Domingues ◽  
Gabriela Silva ◽  
António Almeida ◽  
...  

2016 ◽  
Vol 7 (10) ◽  
pp. 1295-1310 ◽  
Author(s):  
Radosław Januchowski ◽  
Monika Świerczewska ◽  
Karolina Sterzyńska ◽  
Karolina Wojtowicz ◽  
Michał Nowicki ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Radosław Januchowski ◽  
Karolina Wojtowicz ◽  
Patrycja Sujka-Kordowska ◽  
Małgorzata Andrzejewska ◽  
Maciej Zabel

Ovarian cancer is the leading cause of death among gynaecological malignancies. Multiple drug resistance makes cancer cells insensitive to chemotherapy. In this study, we developed six primary ovarian cancer cell lines (W1MR, W1CR, W1DR, W1VR, W1TR, and W1PR) resistant to drugs such as methotrexate, cisplatin, doxorubicin, vincristine, topotecan, and paclitaxel. A chemosensitivity assay MTT test was performed to assess drug cross-resistance. Quantitative real-time polymerase chain reaction and Western blot were also performed to determine mRNA and protein expression of genes involved in chemoresistance. We observed high cross-resistance to doxorubicin, vincristine, and paclitaxel in the cell lines resistant to these agents. We also found a significant correlation between resistance to these drugs and increased expression of P-gp. Two different mechanisms of topotecan resistance were observed in the W1TR and W1PR cell lines. We did not observe any correlation between MRP2 transcript and protein levels. Cell lines resistant to agents used in ovarian cancer treatment remained sensitive to methotrexate. The main mechanisms of drug resistance were due to P-gp expression in the doxorubicin, vincristine, and paclitaxel resistant cell lines and BCRP expression in the topotecan resistant cell line.


2000 ◽  
Vol 36 (15) ◽  
pp. 1984-1990 ◽  
Author(s):  
J. Holford ◽  
P.J. Beale ◽  
F.E. Boxall ◽  
S.Y. Sharp ◽  
L.R. Kelland

2020 ◽  
Author(s):  
Divya RSJB Rana ◽  
Lin Xu ◽  
Jie Zhang

AbstractOvarian cancer is a gynecological cancer of high mortality rate. Most of the ovarian cancer origin from the surface epithelium of the ovaries. Ovarian cancers gain metastatic and invasive properties from various biochemical events taking place during tumorogenesis. MicroRNAs (miRNA) are non-coding RNAs and they have an important function of inhibiting translation of specific mRNAs in the cytoplasm. Present study uses two ovarian cancer cell lines as model to study the differential expression of miR-125a, miR-200a, and miR-199a, and provides indirect proof for possible relationship between miR-199a and its predicted target gene Glycogen Synthase Kinase 3 β (GSK3β). As expected the expression of these three microRNAs are decreased in metastatic ovarian cancer cell line A2780 compared to epithelial ovarian cancer OVCAR3. Reciprocal expression pattern of miR-199a and its predicted target GSK3β was found in two different cell lines providing information on possible inhibitory role of miR-199a against GSK3β.


2021 ◽  
Vol 9 (3) ◽  
pp. 138-147
Author(s):  
Marta Nowacka ◽  
Barbara Ginter-Matuszewska ◽  
Monika Świerczewska ◽  
Michał Nowicki ◽  
Maciej Zabel ◽  
...  

Abstract Resistance to chemotherapy is the main obstacle in contemporary ovarian cancer treatment. The aim of this study was the evaluation of expression of HERC5, IFIH1, SAMD4, MCTP1 and SEMA3A mRNA and assessment their role in resistance to cisplatin, paclitaxel, doxorubicin and topotecan in seven ovarian cancer cell lines. MTT assay was used in resistance assessment. Quantitative polymerase chain reaction was performed to measure the expression levels of the genes. We observed different levels of resistance among cell lines. The resistance was not related to the expression of drug transporters genes. The expression of HERC5 and IFIH1 genes was upregulated, and the expression of SEMA3A gene was downregulated. Expression of SAMD4 was upregulated in PEA1, PEA2, and PEO23 cell lines, and expression of MCTP1 was downregulated in A2780, PEA2, and PEO23 cell lines. Upregulation of HERC5, IFIH1, and SAMD4 and downregulation of SEMA3A and MCTP1 in TOP-resistant ovarian cancer cell lines may suggest some role of those genes in topotecan resistance development.


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