Histone deacetylase 11 suppresses p53 expression in pituitary tumor cells

Cell Biol Int. 2017 Dec;41(12):1290-1295. doi: 10.1002/cbin.10834. Epub 2017 Aug 29.

Abstract

The pathogenesis of pituitary tumors (PT) is unclear. Deregulation of apoptosis is one of the factors involving tumor growth. Histone deacetylases (HDAC) have an active role in multiple cellular activities. This study aims to investigate the role of HDAC in the interference with apoptosis in PT. In this study, PT samples were collected from 20 patients after surgery. The expression of HDAC and p53 was analyzed in the PT samples. PT cell line, AtT-20 cells, was cultured to test the role of HDAC in the regulation of apoptosis in PT cells. The results showed that the high levels of HDAC11 and lower levels of p53 were detected in PT. A negative correlation was detected between the data of HDAC11 and p53. A complex of HDAC11 and HEY1, the gene transcription factor of p53, was detected in the PT cells. Less acetylated HEY1 was found in the PT cells. In addition, lower levels of HEY1 and the gene transcription activities were detected at the PT53 promoter locus. This phenomenon was mimicked by overexpression of HDAC11 in AtT-20 cells. Knockdown of HDAC11 enhanced the p53 expression in AtT-20 cells. In conclusion, HDAC11 interferes with p53 expression in PT cells. The fact suggests that inhibition of HDAC11 has therapeutic potential in the treatment of PT.

Keywords: apoptosis; histone deacetylase; p53; pituitary tumor.

MeSH terms

  • Acetylation
  • Adult
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Female
  • Genes, p53
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Pituitary Neoplasms / enzymology
  • Pituitary Neoplasms / genetics*
  • Pituitary Neoplasms / metabolism
  • Pituitary Neoplasms / pathology
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • HEY1 protein, human
  • Histone Deacetylase Inhibitors
  • RNA, Messenger
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • HDAC11 protein, human
  • Histone Deacetylases