Increased thioredoxin-1 inhibits SSAT expression in MCF-7 human breast cancer cells.
Spermidine/spermine N(1)-acetyltransferase (SSAT) regulates polyamine catabolism. Thioredoxin-1 (Trx-1) is a redox protein that is overexpressed in human cancer leading to increased cell proliferation, decreased apoptosis, and decreased patient survival. We report that SSAT mRNA expression is decreased in Trx-1 transfected MCF-7 human breast cancer cells. There is also a decrease in SSAT enzyme activity and lower putrescine levels but no change in spermine or spermidine levels. The expression of SSAT is regulated by the NF-E2-related factor 2 (Nrf-2) and polyamine modulated factor-1 (PMF-1) transcription factor complex. Trx-1 transfected MCF-7 cells showed decreased Nrf-2/PMF-1 DNA binding without a change in Nrf-2 or PMF-1 protein expression. The results suggest that Trx-1 may play a role in the redox regulation of SSAT expression and polyamine homeostasis that could contribute to the biological effects of Trx-1.
Husbeck
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B
Arizona Cancer Center, University of Arizona, Tucson, AZ 85724-5024, USA.
Stringer
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Gerner
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Powis
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D000123:Acetyltransferases / Q000378:metabolism*; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051267:NF-E2-Related Factor 2; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D011073:Polyamines / Q000737:chemistry; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013879:Thioredoxins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D004247:DNA; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D011073:Polyamines; D012333:RNA, Messenger; D013879:Thioredoxins; D015534:Trans-Activators; D014157:Transcription Factors; D000099228:Diamine N-Acetyltransferase; C495635:NFE2L2 protein, human; C120655:PMF1 protein, human; C491203:TXN protein, human