Methylation of CALCA and CALCB in Pancreatic Ductal Adenocarcinoma

Oxid Med Cell Longev. 2021 Aug 3:2021:2088345. doi: 10.1155/2021/2088345. eCollection 2021.

Abstract

Calcitonin gene-related peptide (CGRP) plays a diverse and intricate role in chronic low-grade inflammation and is closely related to specific cancers. It includes two subtypes, CALCA (αCGRP) and CALCB (βCGRP), of which αCGRP expression accounts for more than 90%. Here, we show that methylation of CALCA and CALCB in pancreatic ductal adenocarcinoma was significantly higher than that in paracancer. Western blot and immunohistochemistry showed that CGRP, p-AKT, and p-CREB in the tumor tissues were lower than those in the paracarcinoma tissues. In vivo, the expressions of p-AKT and p-CREB in the pancreatic tissues of CALCA-KO rats were also lower than those of wild type. Methylation of CALCA and CALCB is increased in pancreatic adenocarcinoma, and under that condition, p-AKT and p-CREB levels were decreased.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Calcitonin Gene-Related Peptide / chemistry
  • Calcitonin Gene-Related Peptide / deficiency
  • Calcitonin Gene-Related Peptide / genetics
  • Calcitonin Gene-Related Peptide / metabolism*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology*
  • CpG Islands
  • DNA Methylation
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Transgenic
  • Signal Transduction

Substances

  • CALCA protein, human
  • CALCB protein, human
  • Proto-Oncogene Proteins c-akt
  • Calcitonin Gene-Related Peptide