HMGA1 is a molecular determinant of chemoresistance to gemcitabine in pancreatic adenocarcinoma.

ABSTRACT:

Purpose

HMGA1 proteins are architectural transcription factors that are overexpressed by pancreatic adenocarcinomas. We previously have shown that RNA interference targeting the HMGA1 gene may represent a potential chemosensitizing strategy in pancreatic adenocarcinoma cells. In this study, we tested the hypothesis that HMGA1 promotes chemoresistance to gemcitabine in pancreatic cancer cells.

Experimental design and results

Stable short hairpin RNA-mediated HMGA1 silencing in BxPC3 and MiaPaCa2 cells promoted chemosensitivity to gemcitabine, with reductions in gemcitabine IC(50) and increases in gemcitabine-induced apoptosis and caspase-3 activation. In contrast, forced HMGA1 overexpression in MiaPaCa2 cells promoted chemoresistance to gemcitabine, with increases in gemcitab

SUBMITTER: Liau SS 

PROVIDER: S-EPMC2652398 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature