Biological and clinical associations of c-jun activation in human breast cancer

✍ Scribed by Julia M. W. Gee; A. Filipa Barroso; Ian O. Ellis; John F. R. Robertson; Robert I. Nicholson

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: French
• Weight: 493 KB
• Volume: 89
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(20000320)89:2<177::aid-ijc13>3.0.co;2-0

✦ Synopsis

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-␣ (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 cjun 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 oestrogenregulated 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.