Cancer cell lines (specifically non-small cell lung cancer) with depleted levels of LKB1 protein.
LKB1 is a serine/threonine kinase gene located on chromosome 19p13.3 and inactivation of LKB1 is present in approximately 30% of non-small cell lung cancer primary tumors and cell lines. LKB1 suppresses tumors, opposite to Akt, by negatively regulating the mammalian target of rapamycin through the activation of AMP-activated protein kinase and the TSC signaling pathway. Emory researchers have developed multiple cancer cell lines that exhibit depleted LKB1. Non-small cell lung cancer cell lines were transfected with lentiviral LKB1 small hairpin RNA. (A negative control construct was transfected in a separate colony of these cells for verification.) LKB1 knockdown significantly impeded or had no effect on overall colony growth dependent on the cell line. LKB1 depletion decreased cell proliferation only in the context of Akt activation, and LKB1 appears to act as a supporter of Akt-mediated phosphorylation of proapoptotic proteins. These cell lines may serve as a valuable tool to study a number of types of cancers as well as to evaluate potential cancer therapeutics.
Publication: Cancer Res. 2008 68: 7270-7277.