By crossing these transgenic mice with a mouse line harboring a lung tissue–specific Cre recombinase transgene driven by a club cell secretory protein gene promoter (CCSP‐iCre), we have found that conditional ERK3 overexpression cooperates with phosphatase and tensin homolog (PTEN) deletion to induce the formation of lung adenocarcinomas (LUADs). Here, PROS1 is linked to lung adenocarcinoma.