PT  - JOURNAL ARTICLE
AU  - AUSRA LUKOSIUTE-URBONIENE
AU  - AUGUSTINA MAZEIKE
AU  - MINTAUTE KAZOKAITE
AU  - GIEDRE SILKUNIENE
AU  - MANTAS SILKUNAS
AU  - VIDMANTAS BARAUSKAS
AU  - GIEDRIUS BARAUSKAS
AU  - ANTANAS GULBINAS
AU  - ALBERTAS DAUKSA
AU  - ZILVINAS DAMBRAUSKAS
TI  - Epigenetic Regulation of APAF-1 Through DNA Methylation in Pancreatic Cancer
AID  - 10.21873/anticanres.14366
DP  - 2020 Jul 01
TA  - Anticancer Research
PG  - 3765--3779
VI  - 40
IP  - 7
4099  - http://ar.iiarjournals.org/content/40/7/3765.short
4100  - http://ar.iiarjournals.org/content/40/7/3765.full
SO  - Anticancer Res2020 Jul 01; 40
AB  - Background/Aim: Apoptotic peptidase activating factor 1 (APAF-1) is essential regulator of apoptosis and inactivation by DNA methylation is common event in numerous cancer types. We investigated the regulation of APAF-1 through DNA methylation in pancreatic cancer. Materials and Methods: Datasets from 44 patients after pancreatoduodenectomy and the pancreatic adenocarcinoma (PDAC) cell lines Capan-2 and MIA PaCa-2 treated with decitabine were analyzed by RT-PCR, immunoblotting, methylation-specific PCR analysis, apoptosis and viability assays to identify effects of APAF-1 regulation. Results: APAF-1 mRNA and protein levels were significantly down-regulated, and APAF-1 methylation status was associated with perineural invasion in PDAC. Decitabine inhibited cell viability and increased apoptosis rates, however failed to restore APAF-1 mRNA and protein levels in cells. Conclusion: APAF-1 gene hypermethylation may contribute to the progression of PDAC through perineural invasion. Decitabine could sensitize pancreatic cancer cells to apoptosis and growth retardation, however, not directly through the APAF-1 demethylation process.