TP53, CDKN2A/P16, and NFE2L2/NRF2 regulate the incidence of pure- and combined-small cell lung cancer in mice.

ABSTRACT: Studies have shown that Nrf2^E79Q/+ is one of the most common mutations found in human tumors. To elucidate how this genetic change contributes to lung cancer, we compared lung tumor development in a genetically-engineered mouse model (GEMM) with dual Trp53/p16 loss, the most common mutations found in human lung tumors, in the presence or absence of Nrf2^E79Q/+. Trp53/p16-deficient mice developed combined-small cell lung cancer (C-SCLC), a mixture of pure-SCLC (P-SCLC) and large cell neuroendocrine carcinoma. Mice possessing the LSL-Nrf2^E79Q mutation showed no difference in the incidence or latency of C-SCLC compared with Nrf2^+/+ mice. However, these tumors did not express NRF2 despite Cre-induced recombination of the LSL-Nrf2^E79Q allele

SUBMITTER: Hamad SH 

PROVIDER: S-EPMC10039451 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature