p53 dosage impedes KrasG12D- and KrasQ61R-mediated tumorigenesis

Author:

Le Roux Özgün,Everitt Jeffery I.,Counter Christopher M.ORCID

Abstract

AbstractMice engineered with G12D versus Q61R mutant of Kras exhibit differences in the number and grade of tumors. Namely, the incidence or grade of oral or forestomach squamous epithelial lesions was more prevalent in the KrasG12Dbackground while hematolymphopoietic disease was more prevalent in the KrasQ61Rbackground. Loss of theTrp53gene encoding p53 enhances the ability of oncogenic Kras to initiate tumorigenesis in carcinogen and genetic models of lung cancer, while an extra copy ofTrp53(Super p53) was recently shown to suppress Kras-induced tumorigenesis in a genetic model of this disease. Given this, we evaluated whether such an extra copy ofTrp53would alter tumorigenesis upon global activation of a modifiedKrasallele engineered with either a G12D or Q61R mutation. We report that an increase in p53 dosage generally reduced tumor number or grade across a number of organs in a manner largely independent of the type of Kras mutation, which was sufficient to extend lifespan in the less aggressive background of aKrasG12Dinitiating mutation.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3