Phospho-Akt expression is high in a subset of Triple Negative Breast Cancer Patients

Authors: Nigel Borg, Shawn Baldacchino, Christian Saliba, Sharon Falzon, James De Gaetano, Christian Scerri, Godfrey Grech

Corresponding: Godfrey Grech (godfrey.grech@um.edu.mt)

Keywords: Triple Negative Breast Cancer, biomarkers, phosphatases, Akt, BRCA1.

Doi: http://dx.medra.org/10.7423/XJENZA.2014.1.08

Issue: Xjenza Online Vol. 2 Iss. 1 - March 2014

Abstract:
The most commonly used biomarkers to predict the response of breast cancer patients to ther- apy are oestrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). Patients positive for these biomarkers are eligible for specic therapies such as anti-oestrogen therapy in the event of ER and PgR positivity, and trastuzumab, a monoclonal antibody, in the case of HER2 positive patients. Patients who are negative for all these three biomarkers, the so-called triple negatives, however, derive little benet from such therapies. The PI3K/Akt pathway is activated in triple negative breast cancer cases, providing a possible target for therapy. The activation of Akt was investigated in Maltese triple negative breast cancer cases using an antibody detecting Akt phosphorylated at serine 473 (anti-Akt pS473). The study showed that 26% of triple negative breast cancer patients had an elevated level of Akt (pS473). Furthermore, FTY720, a pharmacological activator of the phosphatase PP2A, was shown to block Akt activation at a concentration of 1mM, in HCC1937 cells subjected to insulin-like growth factor 1 (IGF-1). Our data dened a subset of triple negative breast cancer patients based on high activity of AKT (pS473). This subset would be eligible for treatment using therapies which target the PI3K/Akt pathway, such as kinase inhibitors or phosphatase activators. In support of this, the BRCA1 mutant cells (HCC1937) were sensitive to the PP2a activator, FTY720. This suggests that FTY720 is a potential drug for use in adjuvant therapy in breast cancer cases having a high Akt (pS473).

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