Accession Number:

ADA610950

Title:

Role of CDK5 as a Tumor Suppressor Gene in Non-Small Cell Lung Cancer

Descriptive Note:

Final rept. 1 June 2013-31 May 2014

Corporate Author:

JOHNS HOPKINS UNIV BALTIMORE MD

Personal Author(s):

Report Date:

2014-08-01

Pagination or Media Count:

7.0

Abstract:

Our goal in this project was to characterize Cdk5 as a tumor suppressor gene in non-small cell lung cancer. We sought to examine this function in the context of two of the major oncogene-driven mechanisms of lung carcinogenesis, activation of Kras and Egfr. To accomplish this, we have generated a novel inducible autochthonous lung cancer mouse model, CE- Cdk5ff, in which mutant Egfr expression is doxycycline inducible, and Cdk5 ablation is mediated by nasally instilled adenoviral-Cre. We also introduced Cdk5ff into a KC lung cancer model, in which Kras is activated, and Cdk5 is simultaneously ablated, by adenoviral-Cre. In both models, ablation of Cdk5 resulted in significant acceleration of lung tumorigenesis. Our confirmation in two in vivo models of clinically germane oncogene-driven lung cancer, involving the oncogenes EGFRL858R and KrasG12D, that Cdk5 deletion accelerates or promotes tumorigenesis, strongly indicate that Cdk5 behaves as a tumor suppressor in lung adenocarcinoma tumorigenesis.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE