Panoply™ Human AKT2 Over-expressing Stable Cell Line

AKT is a serine/threonine kinase comprising three distinct isoforms, known to regulate various biological processes, including tumorigenesis. In this study, researchers utilized cell models, mouse models, and clinical samples to investigate the expression patterns, net effects, and responses to cisplatin treatment of specific AKT isoforms in triple-negative breast cancer (TNBC). Interestingly, analysis of clinical samples revealed relatively high AKT1 expression in primary tumor tissues, whereas AKT2 expression was elevated in lung and liver metastases. Similarly, TNBC cell lines characterized by high proliferation and invasiveness (BT-549 and MDA-MB-231) exhibited high levels of AKT1 and AKT2 expression. By modulating AKT isoform expression in MCF-10A and BT-549 cell lines, the researchers found that the presence of AKT2 was associated with cellular invasiveness, stemness, and drug sensitivity. Silencing AKT2 was observed to suppress the cancer stem cell population (CD44high/CD24low, ALDH1), mammosphere-forming ability, and the potential for invasion and migration in MCF-10A and BT-549 cells. Further investigation demonstrated that the loss of AKT1 isoform function in TNBC cell models and syngeneic mouse models was associated with reduced sensitivity to cisplatin treatment. These findings reveal differential AKT isoform expression in TNBC and confirm that the isoforms play distinct roles regarding stemness, invasiveness, and response to cisplatin therapy.

Here, researchers generated AKT2-overexpressing BT-549 and MCF-10A cell lines, which were validated by mRNA expression analysis. Both AKT2-overexpressing MCF-10A and BT-549 cells exhibited enhanced invasive and migratory capabilities (Figure 1A-F).

Figure 1. AKT2 isoform is correlated with aggressiveness of cells and contributes to metastasis. (Wadhwa B, et al., 2020)