Nuclear factor kappaB transactivation is increased but is not involved in the proliferative effects of thioredoxin overexpression in MCF-7 breast cancer cells.
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-kappaB (NF-kappaB). NF-kappaB 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-kappaB was examined as a mechanism through which Trx overexpression might promote anchorage-independent growth. Constitutive NF-kappaB activity is elevated 4-7-fold in Trx-overexpressing cells. NF-kappaB activity was inhibited in these cells by expressing a dominant-negative mutant of the IkappaB alpha protein (IkappaB alphaM). Expression of IkappaB alphaM in Trx-overexpressing cells dramatically reduced the Trx-associated increase in NF-kappaB 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-kappaB. 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.
Freemerman
A J
AJ
Arizona Cancer Center, University of Arizona, Tucson 85724-5024, USA.
Gallegos
A
A
Powis
G
G
D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D013879:Thioredoxins / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D013879:Thioredoxins