Accession Number : AD1050191


Title :   Investigating Cooperation between KEAP1 and LKB1 Inactivation in Lung Adenocarcinoma


Descriptive Note : Technical Report,01 Aug 2016,31 Jul 2017


Corporate Author : St. Josephs Hospital and Medical Center Phoenix United States


Personal Author(s) : Inge, Landon J


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1050191.pdf


Report Date : 01 Aug 2017


Pagination or Media Count : 15


Abstract : Preliminary analysis in our laboratory reveals concurrent mutation of the LKB1 and KEAP1 tumor suppressors correlate with poor overall survival in lung adenocarcinoma (LA). Phenotypically, there is evidence to suggest that inactivation of KEAP1 may support adaptation to increased oxidative stress that results from LKB1 inactivation. We have found that inactivation of KEAP1 in the background of LKB1 inactivation results in increased growth and resistance to treatment. Further, we have evidence that cross-talk from the PERK kinase, may also further support adaptation to oxidative stress in combination with KEAP1 inactivation in LKB1-deficient LA. These findings suggest that KEAP1/LKB1 inactivation may represent a critical step in LA tumorigenesis and may have a role in therapeutic resistance. We are further exploring these findings using in vivo models.


Descriptors :   carcinoma , lung cancer , mutations , kinases , resistance , neoplasms , genes


Subject Categories : Medicine and Medical Research
      Genetic Engineering and Molecular Biology
      Biochemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE