Transfection with human thioredoxin increases cell proliferation and a dominant-negative mutant thioredoxin reverses the transformed phenotype of human breast cancer cells

Alfred Gallegos, John R. Gasdaska, Charles W. Taylor, Gillian D. Paine-Murrieta, Daniel Goodman, Pamela Y. Gasdaska, Margareta Berggren, Margaret M Briehl, Garth Powis

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148 Citations (Scopus)

Abstract

Thioredoxin, a redox protein with growth factor activity that modulates the activity of several proteins important for cell growth, has been reported to be overexpressed in a number of human primary cancers. In the present study, the effects of stably transfecting mouse NIH 3T3 cells and MCF-7 human breast cancer cells with cDNA for wild-type human thioredoxin or a redox- inactive mutant thioredoxin, Cys32→Ser32/Cys35→Ser35 (C32S/C35S), on cell proliferation and transformed phenotype have been investigated. NIH 3T3 cells transfected with thioredoxin achieved increased saturation densities compared with vector alone-transfected cells, but were not transformed as assessed by tumor formation in immunodeficient mice. Thioredoxin-transfected MCF-7 cells showed unaltered monolayer growth on plastic surfaces compared with vector alone-transfected cells, but exhibited severalfold increased colony formation in soft agarose. Stable transfection of NIH 3T3 and MCF-7 cells with C32S/C35S resulted in inhibition of monolayer growth on plastic surfaces, and up to 73% inhibition of colony formation by MCF-7 cells in soft agarose. When inoculated into immunodeficient mice, thioredoxin-transfected MCF-7 cells formed tumors, although with a 38-57% growth rate compared with vector alone-transfected cells, whereas tumor formation by C32S/C35S-transfected MCF-7 cells was almost completely inhibited. The results of the study suggest that thioredoxin plays an important role in the growth and transformed phenotype of some human cancers. The inhibition of tumor cell growth by the dominant-negative redox-inactive mutant thioredoxin suggests that thioredoxin could be a novel target for the development of drugs to treat human cancer.

Original languageEnglish (US)
Pages (from-to)5765-5770
Number of pages6
JournalCancer Research
Volume56
Issue number24
StatePublished - Dec 15 1996

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Thioredoxins
Transfection
Cell Proliferation
Breast Neoplasms
Phenotype
MCF-7 Cells
Growth
Neoplasms
Oxidation-Reduction
NIH 3T3 Cells
Sepharose
Plastics
Intercellular Signaling Peptides and Proteins
Proteins
Complementary DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gallegos, A., Gasdaska, J. R., Taylor, C. W., Paine-Murrieta, G. D., Goodman, D., Gasdaska, P. Y., ... Powis, G. (1996). Transfection with human thioredoxin increases cell proliferation and a dominant-negative mutant thioredoxin reverses the transformed phenotype of human breast cancer cells. Cancer Research, 56(24), 5765-5770.

Transfection with human thioredoxin increases cell proliferation and a dominant-negative mutant thioredoxin reverses the transformed phenotype of human breast cancer cells. / Gallegos, Alfred; Gasdaska, John R.; Taylor, Charles W.; Paine-Murrieta, Gillian D.; Goodman, Daniel; Gasdaska, Pamela Y.; Berggren, Margareta; Briehl, Margaret M; Powis, Garth.

In: Cancer Research, Vol. 56, No. 24, 15.12.1996, p. 5765-5770.

Research output: Contribution to journalArticle

Gallegos, A, Gasdaska, JR, Taylor, CW, Paine-Murrieta, GD, Goodman, D, Gasdaska, PY, Berggren, M, Briehl, MM & Powis, G 1996, 'Transfection with human thioredoxin increases cell proliferation and a dominant-negative mutant thioredoxin reverses the transformed phenotype of human breast cancer cells', Cancer Research, vol. 56, no. 24, pp. 5765-5770.
Gallegos, Alfred ; Gasdaska, John R. ; Taylor, Charles W. ; Paine-Murrieta, Gillian D. ; Goodman, Daniel ; Gasdaska, Pamela Y. ; Berggren, Margareta ; Briehl, Margaret M ; Powis, Garth. / Transfection with human thioredoxin increases cell proliferation and a dominant-negative mutant thioredoxin reverses the transformed phenotype of human breast cancer cells. In: Cancer Research. 1996 ; Vol. 56, No. 24. pp. 5765-5770.
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