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

Melanie Spears, Carrie A Cunningham, Karen J Taylor, Elizabeth A Mallon, Jeremy Thomas, Gillian R Kerr, Wilma J L Jack, Ian Kunkler, David A Cameron, Udi Chetty, John M S Bartlett

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)481-489
Number of pages9
JournalThe Journal of Pathology
Volume227
Issue number4
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Dive into the research topics of 'Proximity ligation assays for isoform-specific Akt activation in breast cancer identify activated Akt1 as a driver of progression'. Together they form a unique fingerprint.

Cite this