Biological and clinical associations of c-jun activation in human breast cancer.
Sub-units and regulators of the activating protein-1(AP-1) complex have been implicated in breast-cancer biology, therapeutic response and prognosis. This study has immunocytochemically examined the impact of c-jun-protein activation on biological and clinical parameters in human primary breast cancers, employing an antibody specific for the serine 63-phosphorylated c-jun protein. Substantial nuclear immunostaining was commonly apparent, indicative of an activated c-jun pool, with associations with MAP-kinase-signalling elements, e.g., transforming growth factor-alpha (p = 0.04), epidermal growth factor receptor (p = 0.08), phosphorylated erk 1/2 MAP kinase (p = 0.001) and phosphorylated jun kinase (p = 0.05) Little association was noted with c-fos protein, perhaps indicating alternative AP-1 partners for c-jun with a diversity of cellular end-points. This may explain the lack of relationship with proliferation and grade, the imperfect association between increased c-jun activation and poorer survival (p = 0.061), and the apparent relationship with distant metastasis (p = 0.05). While increased c-jun activation related to poorer quality (p = 0.09) and shortened duration of endocrine response in oestrogen-receptor-positive patients (p = 0.018), no generalized effects on oestrogen-regulated gene products were noted, indicating that AP-1 influences on oestrogen-receptor/oestrogen-response element transactivation are unlikely to explain endocrine insensitivity. These data reinforce our belief that elevated AP-1 signalling influences aspects of the breast-cancer phenotype.
Gee
J M
JM
Tenovus Cancer Research Centre, University of Wales College of Medicine, Cardiff, UK. gee@cardiff.ac.uk
Barroso
A F
AF
Ellis
I O
IO
Robertson
J F
JF
Nicholson
R I
RI
D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D002455:Cell Division; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D009363:Neoplasm Proteins / Q000032:analysis*; D018739:Oncogene Proteins v-erbB / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D015398:Signal Transduction; D016019:Survival Analysis; D018808:Transcription Factor AP-1 / Q000032:analysis*
D009363:Neoplasm Proteins; D018739:Oncogene Proteins v-erbB; D016755:Proto-Oncogene Proteins c-jun; D011960:Receptors, Estrogen; D018808:Transcription Factor AP-1