Expression of stress-response and cell proliferation genes in renal cell carcinoma induced by oxidative stress

Am J Pathol. 2000 Jun;156(6):2149-57. doi: 10.1016/S0002-9440(10)65085-7.

Abstract

Ferric nitrilotriacetate induces oxidative damage in renal proximal tubules that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. In search of genes specifically involved in oxystress-induced carcinogenesis, we have applied a modified fluorescent differential display technique to the tumors and an established cell line as well as their non-neoplastic counterparts. We screened approximately 84,000 products. Reverse Northern blotting confirmed differential expression of 20 transcripts, which showed either significant increase, decrease or lack of expression in the RCCs. Five cDNA clones encoded novel products of unknown function. Fifteen cDNA clones were identified by homology search, which included annexin II, Y-box binding protein, ribosomal proteins, heat shock proteins, DNA polymerase, nonmuscle caldesmon (increased); protein tyrosine phosphatase (decreased); selenoprotein P, stromal cell-derived factor 1, intestinal trefoil protein, nicotinamide adenine dinucleotide, reduced form (NADH) dehydrogenase, and insulin-like growth factor binding protein 7 (deleted). Most of the identified genes were associated with stress-response or cellular proliferation. These results suggest that multiple, interactive genetic pathways are involved in carcinogenesis induced by oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence / genetics
  • Blotting, Northern
  • Carcinogens
  • Carcinoma, Renal Cell / chemically induced
  • Carcinoma, Renal Cell / etiology*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Division / genetics
  • Ferric Compounds
  • Gene Expression*
  • Kidney Neoplasms / chemically induced
  • Kidney Neoplasms / etiology*
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Molecular Sequence Data
  • Nitrilotriacetic Acid / analogs & derivatives
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress / genetics
  • Oxidative Stress / physiology*
  • Rats
  • Rats, Wistar
  • Tumor Cells, Cultured

Substances

  • Carcinogens
  • Ferric Compounds
  • Nitrilotriacetic Acid
  • ferric nitrilotriacetate

Associated data

  • GENBANK/AB030380
  • GENBANK/AB030381
  • GENBANK/AB030382
  • GENBANK/AB030383
  • GENBANK/AB030384