Involvement of epigenetic modification of TERT promoter in response to all-trans retinoic acid in ovarian cancer cell lines.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_799FEF056257
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Involvement of epigenetic modification of TERT promoter in response to all-trans retinoic acid in ovarian cancer cell lines.
Journal
Journal of ovarian research
Author(s)
Losi L., Lauriola A., Tazzioli E., Gozzi G., Scurani L., D'Arca D., Benhattar J.
ISSN
1757-2215 (Electronic)
ISSN-L
1757-2215
Publication state
Published
Issued date
10/07/2019
Peer-reviewed
Oui
Volume
12
Number
1
Pages
62
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
All-trans retinoic acid (ATRA) is currently being used to treat hematological malignancies, given the ability to inhibit cell proliferation. This effect seems to be related to epigenetic changes of the TERT (Telomerase Reverse Transcriptase) promoter. When hypomethylated, ATRA-inducible TERT repressors can bind the promoter, repressing transcription of TERT, the rate-limiting component of telomerase. Ovarian carcinomas are heterogeneous tumors characterized by several aberrantly methylated genes among which is TERT. We recently found a hypomethylation of TERT promoter in about one third of serous carcinoma, the most lethal histotype. Our aim was to investigate the potential role of ATRA as an anticancer drug in a sub-group of ovarian carcinoma where the TERT promoter was hypomethylated.
The potential antiproliferative and cytotoxic effect of ATRA was investigated in seven serous ovarian carcinoma and one teratocarcinoma cell lines and the results were compared to the methylation status of their TERT promoter.
The serous ovarian carcinoma cell line OVCAR3, harboring a hypomethylated TERT promoter, was the best and fastest responder. PA1 and SKOV3, two cell lines with an intermediate methylated promoter, revealed a weaker and delayed response. On the contrary, the other 5 cell lines with a highly methylated promoter did not respond to ATRA, indicative of ATRA-resistant cells.
Our results demonstrate an inverse correlation between the methylation level of TERT promoter and ATRA efficacy in ovarian carcinoma cell lines. Although these results are preliminary, ATRA treatment could become a new powerful, personalized therapy in serous ovarian carcinoma patients, but only in those with tumors harboring a hypomethylated TERT promoter.
Keywords
ATRA, Cell lines, DNA methylation, Ovarian cancer, serous ovarian carcinoma, TERT, Telomerase
Pubmed
Web of science
Open Access
Yes
Create date
22/07/2019 17:30
Last modification date
21/11/2022 8:17
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