Re-expression of C/EBP alpha induces CYP2B6, CYP2C9 and CYP2D6 genes in HepG2 cells

FEBS Lett. 1998 Jul 17;431(2):227-30. doi: 10.1016/s0014-5793(98)00746-7.

Abstract

Cytochrome P450 (CYP) activity is very low or even absent in human hepatomas, a phenomenon that is accompanied by low levels of some liver transcription factors, notably C/EBP alpha. To investigate a possible link between this transcription factor and hepatic CYP expression, we have stably transfected HepG2 cells with a C/EBP alpha vector containing a Zn-inducible metallothionein promoter. Expression of functional C/EBP alpha up to liver levels concomitantly increased the mRNAs of several members of the CYP2 family (2B6, 2C9 and 2D6), suggesting that this transcription factor may play a relevant role in controlling the hepatic expression of CYP enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryl Hydrocarbon Hydroxylases*
  • CCAAT-Enhancer-Binding Proteins
  • Carcinoma, Hepatocellular
  • Cells, Cultured
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP2D6 / biosynthesis*
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enzyme Induction
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oxidoreductases, N-Demethylating / biosynthesis*
  • Oxidoreductases, N-Demethylating / genetics
  • RNA, Messenger / metabolism
  • Steroid 16-alpha-Hydroxylase*
  • Steroid Hydroxylases / biosynthesis*
  • Steroid Hydroxylases / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP2D6
  • Steroid 16-alpha-Hydroxylase
  • Oxidoreductases, N-Demethylating