Proximity ligation assays for isoform-specific Akt activation in breast cancer identify activated Akt1 as a driver of progression

Spears, M. et al. (2012) Proximity ligation assays for isoform-specific Akt activation in breast cancer identify activated Akt1 as a driver of progression. Journal of Pathology, 227(4), pp. 481-489. (doi: 10.1002/path.4022)

Abstract

The PI3K/Akt signal transduction pathway plays an important role in cancer progression and cell survival. Akt activation is associated with poor outcome in endocrine-treated breast cancer, whereas high levels of cytoplasmic Akt2 are associated with an improved overall survival. Proximity ligation assays (PLAs) were used to determine quantitative expression levels of isoform-specific activation (phosphorylation) of Akt1 and Akt2 in formalin-fixed, paraffin-embedded cell lines and breast cancer tumour tissues in situ. PLAs demonstrated a range of expression in breast cancer samples for total pAkt1 and pAkt2. High levels of pAkt1 were associated with reduced DRFS (HR: 1.45, 95% CI 1.14–1.83, p = 0.002) and OS (HR: 1.42, 95% CI 1.10–1.83, p = 0.007). When PLA results were combined, patients that had high levels of pAkt1 only had a significantly decreased DRFS (HR: 1.92, 95% CI 1.34–2.76, p = 0.005) and OS (HR: 1.94, 95% CI 1.32–2.86, p = 0.008) compared to other patients. Using PLAs to discriminate activation of Akt1 versus Akt2 suggests that Akt1 drives progression in early breast cancers. In cases where both Akt1/Akt2 are activated, Akt2 may act to reverse this effect. Using PLAs, we have measured activation of Akt1 and Akt2 proteins separately in situ in FFPE breast cancer samples.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mallon, Dr Elizabeth and Bartlett, Prof John
• Authors: Spears, M., Cunningham, C.A., Taylor, K.J., Mallon, E.A., Thomas, J.S.J., Kerr, G.R., Jack, W.J.L., Kunkler, I.H., Cameron, D.A., Chetty, U., and Bartlett, J.M.S.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Pathology
• ISSN: 0022-3417
• ISSN (Online): 1096-9896