Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells.

ABSTRACT:

Background

Notch signalling is essential for the development and maintenance of the colonic epithelium. Its inhibition induces a differentiation phenotype in vivo and reduces adenomas in APCmin mice. Whether Notch signals are also required in colorectal cancer (CRC) has remained elusive. Therefore, 64 CRC cell lines were analysed for the occurrence of proteolytically processed, active Notch.

Results

63 CRC lines contained a fragment with approximately the size of the Notch1 intracellular domain (NICD), which is required for signalling. Subsequent analyses with an antibody that specifically recognises the free Val1744 residue generated by gamma-secretase-mediated cleavage of Notch1 showed that a subset of CRC cells lacks this specific Val1744-NICD. Surprisingly, inhibition of

SUBMITTER: Aleksic T 

PROVIDER: S-EPMC2584637 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature