STAT3 has been found constitutively activated in M14 melanoma cell line, as previously found in other melanoma cells. Using EMSA, DNA affinity experiments, and chromatin immunoprecipitation, STAT3 was found in M14 to bind the alpha2-macroglobulin gene enhancer in association with the protein disulfide isomerase isoform ERp57. The two proteins have also been found to be associated when bound to the SIE sequence in HepG2 cells stimulated by IL-6. In both cases an anti-ERp57 antibody hinders the binding of STAT3 to its consensus sequence on DNA, indicating that ERp57 is a necessary component of the DNA-bound STAT3 complex. Considering the functional association of the two proteins, the overexpression of ERp57 observed in a variety of transformed cells might be relevant to the oncogenic properties of STAT3. (C) 2004 Elsevier Inc. All rights reserved.