Protein kinase A activation confers resistance to trastuzumab in human breast cancer cell lines.

ABSTRACT:

Purpose

Trastuzumab is a monoclonal antibody targeted to the Her2 receptor and approved for treatment of Her2-positive breast cancer. Among patients who initially respond to trastuzumab therapy, resistance typically arises within 1 year. BT/Her(R) cells are trastuzumab-resistant variants of Her2-positive BT474 breast cancer cells. The salient feature of BT/Her(R) cells is failure to downregulate phosphoinositide 3-kinase/Akt signaling on trastuzumab binding. The current work addresses the mechanism of sustained signaling in BT/Her(R) cells, focusing on the protein kinase A (PKA) pathway.

Experimental design

We performed microarray analysis on BT/Her(R) and BT474 cell lines to identify genes that were upregulated or downregulated in trastuzumab-resistant cells. Specific genes

SUBMITTER: Gu L 

PROVIDER: S-EPMC2787631 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature