Transcriptomics

Dataset Information

20

Stage-specific sensitivity to p53 restoration in lung cancer: tumor data


ABSTRACT: Tumorigenesis is a multistep process that results from the sequential accumulation of mutations in key oncogene and tumor-suppressor pathways. The quest to personalize cancer medicine based on targeting these underlying genetic abnormalities presupposes that sustained inactivation of tumor suppressors and activation of oncogenes are required for tumor maintenance. Mutations in the p53 tumor-suppressor pathway are a hallmark of cancer and significant efforts toward pharmaceutical reactivation of mutant p53 pathways are underway1-3. Here we show that restoration of p53 in established murine lung tumors leads to significant but incomplete tumor cell loss specifically in malignant adenocarcinomas but not in adenomas. Also, we define amplification of MAPK signaling as a critical determinant of malignant progression. The differential response to p53 restoration depends on activation of the Arf tumor suppressor downstream of hyperactive MAPK signaling. We propose that p53 naturally limits malignant progression by responding to increased oncogenic signaling, but is unresponsive to low levels of oncogene activity that are sufficient for early stages of lung tumor development. These data suggest that restoration of pathways important in tumor progression, as opposed to initiation, may lead to incomplete tumor regression due to the stage-heterogeneity of tumor cell populations. Overall design: 18 tumors of different grade and treatment status. 6 treated grade 3, 4 treated grade2, 4 untreated grade3, 4 untreated grade2

INSTRUMENT(S): [Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array

ORGANISM(S): Mus musculus  

SUBMITTER: Charles Arthur Whittaker   

PROVIDER: GSE23874 | GEO | 2010-11-24

SECONDARY ACCESSION(S): PRJNA133171

REPOSITORIES: GEO

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