Heregulin-expressing HER2-positive breast and gastric cancer exhibited heterogeneous susceptibility to the anti-HER2 agents lapatinib, trastuzumab and T-DM1.

ABSTRACT:

Background

Overexpression of heregulin, a HER3 ligand, is one mechanism that confers resistance to the anti-HER2 agents trastuzumab and lapatinib. We investigated the impact of heregulin expression on the efficacy of HER2-targeted therapeutic agents, including trastuzumab, trastuzumab emtansine (T-DM1) and lapatinib, in vitro and in vivo and evaluated the heregulin messenger RNA (mRNA) levels in specimens from patients with HER2-positive breast or gastric cancer.

Results

Cell proliferation and apoptosis assays demonstrated that heregulin conferred robust resistance to lapatinib and trastuzumab via HER3-Akt pathway activation followed by survivin overexpression; however, heregulin conferred minimal or no resistance to T-DM1 and paclitaxel. The heregulin mRNA level of one of 1

SUBMITTER: Nonagase Y 

PROVIDER: S-EPMC5356704 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature