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‐1 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, fra1 and fra2). The tumors were characterized with regard to grading, staging, histology, steroid‐receptor‐expression status and c‐erbB2/neu expression. For comparison, normal breast‐tissue samples, human breast‐cancer cell lines (T47D and MDA‐MB231) 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‐1 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‐1 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. Int. J. Cancer (Pred. Oncol.) 84:533–538, 1999. © 1999 Wiley‐Liss, Inc.

Specific c-Jun target genes in malignant melanoma

“…Kim and colleagues 30 detected under-expression of FosB in pancreatic cancer tissues with lymph node metastasis compared to pancreatic cancer tissues without lymph node metastasis and showed that decreased expression of FosB is associated with reduced survival. In contrast, other studies showed a bipolar FosB expression pattern in breast cancer, 31 whereas our study indicated high FosB expression in melanoma cell lines compared to NHEMs. Moreover, the gene product of NFATC2 was found to be functionally important in malignant melanoma, as it inhibits apoptosis.…”

C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma

“…Proteins were lysed in ice-cold sample buffer (50 mM Tris pH 6.8, 1% sodium dodecyl sulphate (SDS), 10% sucrose and 10 ml ml À1 protease inhibitor cocktail (Sigma, Taufkirchen, Germany)), and protein concentration was determined following the standard protocols and using bovine serum albumin protein standards as described previously (Bamberger et al, 1999;Milde-Langosch et al, 2005).…”

“…Band intensities were quantified by densitometry (GS-700 Imaging Densitometer, BioRad, Munich, Germany). Intensities of the specific protein bands were calculated as percent intensity of the control sample and corrected for equal actin loading as previously described (Bamberger et al, 1999).…”

“…Besides c-Fos, FosB, Fra-1 and Fra-2 have also been shown to have a function in progression of various tumour types: FosB is downregulated in poorly differentiated mammary carcinomas (Bamberger et al, 1999), whereas Fra-1 and, partly, Fra-2 overexpression leads to enhanced tumour cell motility and invasion in breast cancer, colorectal cancer and mesothelioma (Milde-Langosch, 2005).…”

Expression des „activated leukocyte cell adhesion molecule“ im Mammakarzinom

“…Der Proteingehalt im Überstand wurde mit einem "Bicinchoninic-acid"-(BCA-)Protein-Assay ermittelt. WesternBlot-Analysen wurden, wie beschrieben [7], unter Verwendung von 20 μg Protein/Spur in einem 8%igen Polyacrylamidgel durchgeführt. Die Proteine wurden auf eine PVDF-Membran (Immobilon P, Millipore, Eschborn) übertragen und für 1 h mit dem NCL-CD166-Antikörper in einer Verdünnung 1:400 inkubiert.…”