Down-regulation of MDR1 by epigenetic alteration in human epithelial ovarian cancer cells

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16556-e16556
Author(s):  
Y. Kawakami ◽  
K. Miyamoto ◽  
K. Takehara ◽  
M. Kumagai ◽  
O. Samura ◽  
...  

e16556 Background: Ovarian cancer is one of the most lethal malignancies in women. Despite recent studies of many oncogenes and tumor-suppressor genes concerning about its progression, the details of ovarian cancer biology still remains to be unclear. P-glycoprotein (P-gp) encoded by the MDR1 gene is a membrane protein that can export many kinds of antineoplastic agents from cells, and overexpression of P-gp has been reported to be implicated in treatment failure in cancer. DNA methylation, a major epigenetic process, can affect every step in carcinogenesis as well as genetic alterations. The contribution of such epigenetic alteration to the expression of MDR1 remains largely unexplored in human ovarian cancer. Methods: In this study, we evaluated the DNA methylation status of the MDR1 gene by methylation-specific PCR. Then, the expression of MDR-1 mRNA and protein in primary epithelial ovarian cancer specimens were evaluated by real-time RT-PCR and immunohistochemistry using anti-mouse P-gp F4 monoclonal antibody, respectively. The correlation between these results and clinicopathological features was examined. Results: MDR1 was hypermethylated in 12 of 12 (100%) ovarian cancer cell lines, and 5 of 13 (38%) primary ovarian cancers by methylation-specific PCR analysis. MDR1 mRNA expression was subsequently found to be lost in ovarian cancer cell lines with methylation by both real-time RT-PCR and immunohistochemistry. Thus, MDR1expression was associated with the DNA methylation status of the MDR1 gene. Conclusions: In conclusion, MDR1 was frequently hypermethylated in human ovarian cancers. Our results suggest that epigenetic regulation might play a role in the expression of MDR1 and clinical treatment outcomes in human ovarian cancer. No significant financial relationships to disclose.

2000 ◽  
Vol 85 (10) ◽  
pp. 3509-3512 ◽  
Author(s):  
Gabor Halmos ◽  
Baodong Sun ◽  
Andrew V. Schally ◽  
Francine Hebert ◽  
Attila Nagy

ABSTRACT. Characteristics of receptors for somatostatin (SST) analog RC-160 on 17 surgical specimens of human epithelial ovarian cancer and two human ovarian cancer lins were determined by ligand competition assays. The expression of mRNA for four SST receptor subrypes (sst1, sst3, sst2A, sst5) was investigated by RT-PCR. Thirteen of 17 specimens (76%) exhibited high affinity binding sites for RC-160 with Kd = 6.55 nmol/L and a Bmax = 575.4 fmol/mg membrane protein. Specific receptors for RC-160 were also found in xenografts of OV-1063 and UCI-107 human ovarian cancer lines. The mRNA for sst1 was detected in 65% of the ovarian cancer specimens, while the incidence ov sst2A, sst3, and sst5 was 65%, 41% and 24%, respectively. Both ovarian cancer cell lines also expressed mRNA for these four subtypes. The presence of these SST receptor subtypes in human ovarian cancers allows the use of SST analogs and their radionuclide and cytoxic derivatives for the diagnosis and treatment of this malignancy.


Oncogene ◽  
2008 ◽  
Vol 27 (19) ◽  
pp. 2737-2745 ◽  
Author(s):  
H Sasaki ◽  
J Hayakawa ◽  
Y Terai ◽  
M Kanemura ◽  
A Tanabe-Kimura ◽  
...  

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Qin Zhang ◽  
Shuxiang Zhang

Ovarian cancer is one of the leading causes of death among gynecological malignancies. Increasing evidence indicate that dysregulation of microRNAs (miRNAs) plays an important role in tumor radioresistance. The aim of the present study is to investigate whether microRNA-214 (miR-214) was involved in radioresistance of human ovarian cancer. Here, we showed that miR-214 was significantly up-regulated in ovarian cancer tissues and radioresistance ovarian cancer cell lines. Transfection of miR-214 agomir in radiosensitive ovarian cancer cell lines promoted them for resistance to ionizing radiation, whereas transfection of miR-214 antagomir in radioresistance ovarian cancer cell lines sensitized them to ionizing radiation again. Furthermore, we found miR-214 effectively promoted tumor radioresistance in xenograft animal experiment. Western blotting and quantitative real-time PCR demonstrated that miR-214 negatively regulated PTEN in radioresistance ovarian cancer cell lines and ovarian cancer tissues. Taken together, our data conclude that miR-214 contributes to radioresistance of ovarian cancer by directly targeting PTEN.


PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0185111 ◽  
Author(s):  
Vijayalakshmi N. Ayyagari ◽  
Paula L. Diaz-Sylvester ◽  
Tsung-han Jeff Hsieh ◽  
Laurent Brard

2020 ◽  
Vol 16 (5) ◽  
pp. 524
Author(s):  
Rajeswary Hari ◽  
Priyadurairaj ◽  
PalagatiRohith Kumar Reddy ◽  
Palaniyandi Thiruvanavukkarasu ◽  
Sindhu Rajesh ◽  
...  

2017 ◽  
Vol 41 (18) ◽  
pp. 10438-10446
Author(s):  
E. Tsovaltzi ◽  
E. Malamidou-Xenikaki ◽  
P. Dalezis ◽  
A. Hatzidimitriou ◽  
T. Lazarides ◽  
...  

Piano-stool Ru(ii) complexes incorporating 2-hydroxymethylidene-indene-1,3-dione ligands exhibit promising anticancer activity against four human ovarian cancer cell lines.


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