DARPP-32 increases interactions between epidermal growth factor receptor and ERBB3 to promote tumor resistance to gefitinib.

ABSTRACT:

Background & aims

Dopamine and adenosine 3',5'-cyclic monophosphate-regulated phosphoprotein, Mr 32000 (DARPP-32), is overexpressed during gastric carcinogenesis. Gastric tumors can become resistant to gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR). We investigated the role of DARPP-32 in gastric tumor resistance to gefitinib.

Methods

Cell survival was determined by clonogenic survival and ATP-Glo Viability Assays. Apoptosis was assessed by Annexin-V and immunoblot analyses. The association between DARPP-32 and EGFR was evaluated by immunofluorescence and co-immunoprecipitation assays. Findings were validated in mice with gastric xenograft tumors. DARPP-32 expression was reduced using small hairpin RNAs in the human gastric cancer cell lines SNU-16 an

SUBMITTER: Zhu S 

PROVIDER: S-EPMC3202055 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature