Expression pattern of the ap-1 family in breast cancer: Association of fosb expression with a well-differentiated, receptor-positive tumor phenotype

Abstract

In the present study, the expression of members of the AP-I family of transcription factors in breast tumors (n = 53) was investigated by Western blot with antibodies specific for each of the AP-1 family members (c-jun, junB, junD and c-fos, fosB, fral and fra2). The tumors were characterized with regard to grading, staging, histology, steroid-receptorexpression status and c-erbB2/neu expression. For comparison, normal breast-tissue samples, human breast-cancer cell lines (T47D and MDA-MB23I) and the transformed human breast epithelial cell line HBL100 were also analyzed. For c-jun, junB, c-fos and fra2, a relatively uniform expression pattern without significant differences among tumors was observed. junD-protein amounts varied strongly in the tumor specimens. fosB-expression levels also varied strongly in the tumors, weak/absent expression being found in 47%, while 45% exhibited strong/very strong levels of expression. While none of the other AP-I family members showed significant correlations with clinico-pathological tumor parameters or receptor status, expression of fosB was found to correlate significantly with positive steroid-hormone-receptor status (in the tumors and the cell lines) and a more differentiated tumor phenotype. Expression of 2 fra-1 -specific bands of 33 and 36.5 kDa showed significant negative correlation with fosB expression, as well as with estrogen-receptor status and differentiation. We conclude that strong differences in the expression pattern of AP-I family members are present in breast tumors, and that certain members of this family, such as fosB and fra-1, might be involved in the pathogenesis of these tumors. © 1999 Wiley-Liss, Inc.