Chemotherapy-induced activation of ADAM-17: a novel mechanism of drug resistance in colorectal cancer.

ABSTRACT:

Purpose

We have shown previously that exposure to anticancer drugs can trigger the activation of human epidermal receptor survival pathways in colorectal cancer (CRC). In this study, we examined the role of ADAMs (a disintegrin and metalloproteinases) and soluble growth factors in this acute drug resistance mechanism.

Experimental design

In vitro and in vivo models of CRC were assessed. ADAM-17 activity was measured using a fluorometric assay. Ligand shedding was assessed by ELISA or Western blotting. Apoptosis was assessed by flow cytometry and Western blotting.

Results

Chemotherapy (5-fluorouracil) treatment resulted in acute increases in transforming growth factor-alpha, amphiregulin, and heregulin ligand shedding in vitro and in vivo that correlated with significa

SUBMITTER: Kyula JN 

PROVIDER: S-EPMC2896550 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature