Gene Expression Analysis Indicates Divergent Mechanisms in DEN-Induced Carcinogenesis in Wild Type and Bid-Deficient Livers

PLoS One. 2016 May 19;11(5):e0155211. doi: 10.1371/journal.pone.0155211. eCollection 2016.

Abstract

Bid is a Bcl-2 family protein. In addition to its pro-apoptosis function, Bid can also promote cell proliferation, maintain S phase checkpoint, and facilitate inflammasome activation. Bid plays important roles in tissue injury and regeneration, hematopoietic homeostasis, and tumorigenesis. Bid participates in hepatic carcinogenesis but the mechanism is not fully understood. Deletion of Bid resulted in diminished tumor burden and delayed tumor progression in a liver cancer model. In order to better understand the Bid-regulated events during hepatic carcinogenesis we performed gene expression analysis in wild type and bid-deficient mice treated with a hepatic carcinogen, diethylnitrosamine. We found that deletion of Bid caused significantly fewer alterations in gene expression in terms of the number of genes affected and the number of pathways affected. In addition, the expression profiles were remarkably different. In the wild type mice, there was a significant increase in the expression of growth regulation-related and immune/inflammation response-related genes, and a significant decrease in the expression of metabolism-related genes, both of which were diminished in bid-deficient livers. These data suggest that Bid could promote hepatic carcinogenesis via growth control and inflammation-mediated events.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • BH3 Interacting Domain Death Agonist Protein / metabolism*
  • Carcinogenesis
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics*
  • Cell Proliferation
  • Diethylnitrosamine
  • Female
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Inflammation
  • Liver / drug effects*
  • Liver / metabolism
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • Bid protein, mouse
  • Diethylnitrosamine