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Nuclear Factor B Transactivation Is Increased But Is Not Involved in the Proliferative Effects of Thioredoxin Overexpression in MCF-7 Breast Cancer Cells¹

Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724-5024

Thioredoxin (Trx) is a small redox-active protein that provides reducing equivalents for key cysteine residues of proteins through thiol-disulfide exchange, such as the transcription factor nuclear factor-B (NF-B). NF-B activation has been associated previously with cell growth and the inhibition of apoptosis. We have shown in earlier studies that overexpression of Trx in MCF-7 cells increases anchorage-independent growth. In this study, the activation of NF-B was examined as a mechanism through which Trx overexpression might promote anchorage-independent growth. Constitutive NF-B activity is elevated 4–7-fold in Trx-overexpressing cells. NF-B activity was inhibited in these cells by expressing a dominant-negative mutant of the IB protein (IBM). Expression of IBM in Trx-overexpressing cells dramatically reduced the Trx-associated increase in NF-B activity but did not affect anchorage-dependent or -independent growth. The results suggest that increased growth in MCF-7 cells overexpressing Trx is not mediated by increased activation of the transcription factor, NF-B. Additionally, activator protein-1 (AP-1), another transcription factor associated with growth, was increased up to 10-fold in Trx-overexpressing cells. Thus, AP-1 activation might contribute to the growth-promoting effect of Trx.

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