Journal
CANCER RESEARCH
Volume 67, Issue 16, Pages 7695-7702Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-07-0484
Keywords
-
Categories
Funding
- NCI NIH HHS [P50 CA070907, P01 CA095471, P01CA95471, P50 CA070907-10, P50CA70907, P01 CA095471-010001] Funding Source: Medline
- NCRR NIH HHS [C06 RR-15437, C06 RR015437] Funding Source: Medline
Ask authors/readers for more resources
Some non-small cell lung cancers (NSCLC) with epidermal growth factor receptor (EGFR) tyrosine kinase domain mutations require altered signaling through the EGFR for cell survival and are exquisitely sensitive to tyrosine kinase inhibitors. EGFR down-regulation was impaired in two NSCLCs with EGFR tyrosine kinase domain mutations. The mutant receptors were poorly ubiquitylated and exhibited decreased association with the ubiquitin ligase Cbl. Overexpression of Cbl increased the degradation of EGFR. Treatment with geldanamycin, an inhibitor of the chaperone heat shock protein 90, also increased both wild-type and mutant EGFR degradation without affecting internalization. The down-regulation of the mutant EGFRs was still impaired when they were stably expressed in normal human bronchial epithelial cells. Thus, the mutations that altered signaling also decreased the interaction of EGFRs with the mechanisms responsible for endosomal sorting.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available