Heterozygous Atmin deletion significantly increased tumor cell proliferation, tumor burden, and tumor grade in the LSL-KRasG12D; Trp53 F/F (KP) mouse model of lung adenocarcinoma, identifying ATMIN as a haploinsufficient tumor suppressor.
We report that mouse LSL-Kras<sup>G12D</sup>;Trp53<sup>fl/fl</sup> (KP)-mediated lung adenocarcinoma (LADC) tumorigenesis can proceed through both PKCι-dependent and PKCι-independent pathways.
In addition, AM isolated from Kras<sup>LSL-G12D</sup> animals and transduced by Ad5-CMV-Cre <i>ex vivo</i> displayed prolonged survival <i>in vitro</i> and increased the growth of murine lung adenocarcinoma CMT/167 cells when co-injected in an orthotopic flank model.
In Kras<sup>LSL-G12D/WT</sup>, Kras<sup>LSL-G12D/WT</sup>; Lkb1<sup>Flox/Flox</sup> and Kras<sup>LSL-G12D/WT</sup>; p53<sup>Flox/Flox</sup> mouse models of lung adenocarcinoma, we monitored an impaired progression of tumors upon RANKL blockade.
In the present study, we used a transcriptomics approach to elucidate the mechanism of Snail-mediated tumor growth promotion in a <i>Kras<sup>LSL-G12D/+</sup>;p53<sup>fl/fl</sup></i> mouse model of lung adenocarcinoma.
Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in Kras(G12D-LSL) mice.
Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras(LSL-G12D/+);p53(flox/flox) mice initiates lung adenocarcinoma development.