@article {LUKOSIUTE-URBONIENE3765, author = {AUSRA LUKOSIUTE-URBONIENE and AUGUSTINA MAZEIKE and MINTAUTE KAZOKAITE and GIEDRE SILKUNIENE and MANTAS SILKUNAS and VIDMANTAS BARAUSKAS and GIEDRIUS BARAUSKAS and ANTANAS GULBINAS and ALBERTAS DAUKSA and ZILVINAS DAMBRAUSKAS}, title = {Epigenetic Regulation of APAF-1 Through DNA Methylation in Pancreatic Cancer}, volume = {40}, number = {7}, pages = {3765--3779}, year = {2020}, doi = {10.21873/anticanres.14366}, publisher = {International Institute of Anticancer Research}, abstract = {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.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/40/7/3765}, eprint = {https://ar.iiarjournals.org/content/40/7/3765.full.pdf}, journal = {Anticancer Research} }