Jun and Fos family protein expression in human breast cancer: correlation of protein expression and clinicopathological parameters.
OBJECTIVE
The activator protein-1 (AP-1) is a dimeric transcription factor formed by members of the Jun and Fos protein family. AP-1 plays a role in a variety of physiological functions including cell proliferation and differentiation, although both c-Jun and c-Fos have also been implicated in oncogenic transformation and tumor progression. To further elucidate the role of AP-1 in breast cancer, we have investigated the expression of the AP-1 proteins c-Jun, JunB, JunD, phosphorylated c-Jun, c-Fos, Fral, Fra2 and the tumor supressor protein p53.


METHODS
Protein expression was evaluated on a breast cancer tissue microarray with 58 lymph node positive or negative breast cancer specimens, 29 corresponding lymph node metastases, and 11 tissue samples from surrounding tumor-free tissue, each cored as triplicate. Jun and Fos protein family expression was evaluated by immunohistochemistry and was correlated with clinicopathological parameters.


RESULTS
High expression levels were observed for c-Jun, JunD, c-Fos and Fra2, whereas JunB and Fral exhibited lower staining. c-Jun protein expression was correlated to Fral staining (p = 0.007, Kendall's Tau) and Fral was further associated with c-Fos (p < 0.001), JunD (p = 0.001) and Fra2 (p = 0.011) expression. JunD expression correlated with c-Fos (p < 0.001), JunB (p = 0.035) and c-Jun (p = 0.05). Activated c-Jun correlated with c-Fos expression (p = 0.041). JunB was negatively correlated to tumor stage, (p = 0.093, corr coeff. = -0.293, Spearman's correlation) but was significantly increased in nodal negative tumors (p = 0.004, Mann Whitney test). In addition, increased Fral expression showed a trend towards an increased overall survival (p = 0.077, RR = 0.534, Cox regression).


CONCLUSIONS
Our results suggest an important role for JunB and Fral in the biological behavior of malignant breast tumors.
Langer
S
S
Department of Obstetrics and Gynecology, Division of Senology, Medical University of Vienna, Austria.
Singer
C F
CF
Hudelist
G
G
Dampier
B
B
Kaserer
K
K
Vinatzer
U
U
Pehamberger
H
H
Zielinski
C
C
Kubista
E
E
Schreibner
M
M
D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D005260:Female; D051921:Fos-Related Antigen-2 / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000099169:Fos-Related Antigen 1
D014408:Biomarkers, Tumor; D051921:Fos-Related Antigen-2; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016159:Tumor Suppressor Protein p53; D000099169:Fos-Related Antigen 1; C497872:FOSL2 protein, human