Abstract P111: DISTINCT EXPRESSION OF AKT ISOFORMS IN TRIPLE NEGATIVE BREAST CANCERS AND ROLES OF AKT ISOFORMS IN CISPLATIN SENSITIVITY

Abstract AKT, a serine threonine kinase, exists in three different isoforms and is known for regulating several biological processes including tumorigenesis. In this study, we investigated the expression and net effect of the individual isoforms in triple negative breast cancers and response to cisplatin treatment using cellular, mice models and clinical samples. Interestingly, analysis of the expressions of AKT isoforms in clinical samples showed relatively higher expression of AKT1 in primary tissues; whereas lung and liver metastatic samples showed elevated expression of AKT2. Similarly, triple-negative breast cancer cell lines, BT-549 and MDA-MB-231, with high proliferative and invasive properties, displayed higher expression levels of AKT1/2. By modulating AKT isoform expression in MCF-10A and BT-549 cell lines, we found that presence of AKT2 was associated with invasiveness, stemness and sensitivity to drug treatment. It was observed that the silencing of AKT2 suppressed the cancer stem cell populations (CD44 high, CD24 low) in MCF-10A and BT-549 cells. The decrease in cisplatin treatment response in shAKT1 cells was allied with the upregulation in the expression of transporter protein ABCG2. In conclusion, our study demonstrated the varied expression of AKT isoforms in triple-negative breast cancers and also confirmed differential role of isoforms in stemness, invasiveness and response towards the cisplatin treatment. Citation Format: Bhumika Wadhwa, Jyoti Singh, Nisha Chandak, Saranga V, Hitesh Vasiyani, Rajesh Singh. DISTINCT EXPRESSION OF AKT ISOFORMS IN TRIPLE NEGATIVE BREAST CANCERS AND ROLES OF AKT ISOFORMS IN CISPLATIN SENSITIVITY [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P111.