Targeting nucleophosmin 1 represents a rational strategy for radiation sensitization.

ABSTRACT:

Purpose

To test the hypothesis that small molecule targeting of nucleophosmin 1 (NPM1) represents a rational approach for radiosensitization.

Methods and materials

Wilde-type and NPM1-deficient mouse embryo fibroblasts (MEFs) were used to determine whether radiosensitization produced by the small molecule YTR107 was NPM1 dependent. The stress response to ionizing radiation was assessed by quantifying pNPM1, γH2AX, and Rad51 foci, neutral comet tail moment, and colony formation. NPM1 levels in a human-derived non-small-cell lung cancer (NSCLC) tissue microarray (TMA) were determined by immunohistochemistry. YTR107-mediated radiosensitization was assessed in NSCLC cell lines and xenografts.

Results

Use of NPM1-null MEFs demonstrated that NPM1 is critical for DNA double-

SUBMITTER: Sekhar KR 

PROVIDER: S-EPMC4105849 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature