Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia

Margareta Berggren, Alfred Gallegos, John R. Gasdaska, Pamela Y. Gasdaska, James Warneke, Garth Powis

Research output: Contribution to journalArticle

261 Scopus citations

Abstract

Thioredoxin and thioredoxin reductase are redox proteins that have been implicated in the control of cell proliferation and transformation. We report the levels and activity of these proteins and their mRNAs in human primary tumors and tumor cell fines. Half of human primary colorectal carcinomas (5/10) examined had increased thioredoxin mRNA, of 3- to over 100-fold, compared to adjacent normal colonic mucosa from the same subject. Thioredoxin reductase protein and activity were increased an average of 2-fold in human colorectal tumors compared to normal mucosa. A number of human hematologic and solid tumor cell lines were studied and showed a 10-fold range of thioredoxin mRNA and a 23-fold range of thioredoxin reductase mRNA. Increased proliferation and hypoxia are factors that might contribute to the increased expression in solid tumors. We found that serum stimulation of growth arrested MCF-7 breast cancer cells caused a 59% increase in thioredoxin mRNA and a 62% increase in thioredoxin reductase mRNA by 24 hours. Exposure of HT-29 colon cancer cells to hypoxia resulted in a 14-fold increase in thioredoxin mRNA by 16 hours, and a transient 4-fold increase in thioredoxin reductase mRNA at 1 hour that had returned to control levels by 8 hours. Cancer cells were found to release thioredoxin into the medium at rates between 1 to 2 pmole/106 cells/3 hours. The rate of secretion was not, however, related to cellular-levels of thioredoxin. The results of the study show that the expression of thioredoxin and thioredoxin reductase are increased several fold in some human solid tumors compared to normal tissue. Secretion of thioredoxin, which is known to have a direct growth stimulating activity, by human tumor cells might lead to the stimulation of cancer cell growth.

Original languageEnglish (US)
Pages (from-to)3459-3466
Number of pages8
JournalAnticancer research
Volume16
Issue number6 B
StatePublished - Dec 1 1996

Keywords

  • Cell growth
  • Hypoxia
  • Thioredoxin
  • Thioredoxin reductase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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