Abstract 3053: PTEN as a double-edged sword regulates EGFRL858R-induced lung cancer progression

Abstract Lung cancer is the major cause of death worldwide. Activation of oncogenes or inhibition of tumor suppressors causes cancer formation. Previous studies have indicated that Pten, as a tumor suppressor, inhibits cancer formation. In this study, we studied the role of Pten in EGFRL858R-induced lung cancer in vivo. Interestingly, loss of Pten increased bronchial cell hyperplasia but decreased alveolar cell hyperplasia in EGFRL858R*Pten−/−-induced lung cancer. Syatematic analysis of gene expression by RNA-seq showed that a number of genes related to ciliogenesis were upregulated in EGFRL858R*Pten−/−-induced lung cancer and subsequently showed that bronchial ciliated cells were hyperplastic. Several critical ciliogenesis-related genes, such as mucin5a, DNAI2 and DNAI3, were found to be regulated by NR2F1. Next, NR2F1 was found to be inhibited by overexpression of Pten, indicating that Pten negatively regulates NR2F1, thereby inhibiting the expression of ciliogenesis-related genes and leading to the inhibition of bronchial cell hyperplasia during EGFRL858R-induced lung cancer progression. In addition, we also found that Pten decreased Akt phosphorylation in A549, Kras mutant, and H1299 cells but increased Akt phosphorylation in PC9, EGFRL858R, and H1299L858R cells, suggesting that Pten may function as a tumor suppressor and an oncogene in lung cancers with Kras mutation and EGFR mutation, respectively. PTEN acts as a double-edged sword that differentially regulates EGFRL858R-induced lung cancer progression in different genomic backgrounds. Understanding the Pten in lung cancer with different genetic backgrounds will be beneficial for therapy in the future. Citation Format: Jan-Jong Hung. PTEN as a double-edged sword regulates EGFRL858R-induced lung cancer progression abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3053.