Endogenous tumor necrosis factor promotes resistance to cellular stresses by inducing the metallothionein-1A gene

Anticancer Res. 2002 Nov-Dec;22(6C):4059-63.

Abstract

Background: Endogenous tumor necrosis factor (enTNF) acts as a resistance factor against anticancer drugs, heat and exogenous TNF via induction of manganous superoxide dismutase (MnSOD) and heat shock protein 72 (HSP72), while the details of interaction with other molecules are not fully understood. We compared mRNA expression of various genes between MIAPaCa-2 human pancreatic cancer cells and M5 cells transduced with nonsecretory-type TNF gene expression vector.

Materials and methods: The expression of certain mRNAs between human pancreatic cancer MIAPaCa-2 cells and M5 cells was compared using fluorescent differential display.

Results: Of 140 bands obtained by gel electrophoresis, 53 bands showed patterns differing between MIAPaCa-2 and M5 cells. Among these bands, sequence analysis and RT-PCR identified strong mRNA expression for metallothionein-1A, a scavenger of reactive oxygen species, in transduced M5 cells.

Conclusion: Metallothionein-1A could be induced by enTNF, resulting in resistance against various cellular stresses.

MeSH terms

  • Base Sequence
  • Drug Resistance, Neoplasm
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Metallothionein / biosynthesis*
  • Metallothionein / genetics
  • Molecular Sequence Data
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transduction, Genetic
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Metallothionein