Constitutively active Akt1 cooperates with KRas(G12D) to accelerate in vivo pancreatic tumor onset and progression

Neoplasia : an International Journal for Oncology Research
Toya M AlburyDeborah A Altomare

Abstract

Pancreatic adenocarcinoma is a deadly disease characterized by metastatic progression and resistance to conventional therapeutics. Mutation of KRAS is the most frequent early event in pancreatic tumor progression. AKT isoforms are frequently activated in pancreatic cancer, and reports have implicated hyperactivation of AKT1, as well as AKT2, in pancreatic tumor formation. The objective here is to delineate the role of AKT in facilitating in vivo pancreatic tumor progression in the context of KRAS mutation and predisposition to pancreatic cancer. Mice with Akt1 and KRas mutant alleles expressed using the pancreas Pdx promoter were mated to characterize the incidence and frequency of histologic and genetic alterations known to occur commonly in human pancreatic ductal adenocarcinoma. Active Akt1 (Akt1(Myr), containing a myristoylation sequence) cooperated with active mutant KRas(G12D) to accelerate pancreatic carcinoma onset and progression and increase phosphorylation of downstream effectors in the Akt pathway. Mucin and smooth muscle actin expression was found in and around pancreatic intraepithelial neoplasms (PanINs), and accelerated time to metastasis was found in Akt1(Myr)/KRas(G12D) mice. In contrast to prior reports of pa...Continue Reading

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Citations

Mar 20, 2016·Neoplasia : an International Journal for Oncology Research·Yiannis DrososBeatriz Sosa-Pineda
Oct 22, 2015·The Journal of Endocrinology·Toya M Albury-WarrenDeborah A Altomare
Jul 15, 2015·Advances in Biological Regulation·Romain BaerJulie Guillermet-Guibert
Sep 6, 2017·Scientific Reports·Krishna KanhaiyaIon Petre
Mar 9, 2017·Nature Reviews. Gastroenterology & Hepatology·Peter Storz
Aug 16, 2017·Nature Communications·Tamara ZaytouniNada Y Kalaany
Jun 20, 2020·Cell Communication and Signaling : CCS·Sarah B GittoDeborah A Altomare
Mar 26, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rania BassiouniAnnette R Khaled
Mar 7, 2021·Cancer Science·Nozomi YachidaTakayuki Enomoto
Aug 28, 2021·Life·Graziana DigiacomoAndrea Cavazzoni
Jul 6, 2021·Signal Transduction and Targeted Therapy·Shun WangQiong-Zhu Dong

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Methods Mentioned

BETA
transgenic
PCRs
PCR
electrophoresis
genotyping
myristoylation

Software Mentioned

JumpStart
GraphPad Prism

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