Combined PDGFR and HDAC Inhibition Overcomes PTEN Disruption in Chordoma.

ABSTRACT:

Background

The majority of chordomas show activation of the platelet-derived growth factor receptor (PDGFR). Based on in vitro intertumoral variation in response to recombinant PDGF protein and PDGFR inhibition, and variable tumor response to imatinib, we hypothesized that chordomas resistant to PDGFR inhibition may possess downstream activation of the pathway.

Methods

Molecular profiling was performed on 23 consecutive chordoma primary tissue specimens. Primary cultures established from 20 of the 23 specimens, and chordoma cell lines, UCH-1 and UCH-2, were used for in vitro experiments.

Results

Loss of heterozygosity (LOH) at the phosphatase and tensin homolog (PTEN) locus was observed in 6 specimens (26%). PTEN disruption statistically correlated with increased Ki-6

SUBMITTER: Lee DH 

PROVIDER: S-EPMC4527706 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature