Abstract 218: MEOX-1 as a novel cancer stem cell target for treatment of trastuzumab-resistant Her2+ breast cancers

Introduction: Previous studies showed that 60-80% of Her2+ breast cancers develop Trastuzumab-resistance after one year treatment and more than 50% of Her2+ Trastuzumab-resistant breast cancers have PTEN deletion and increased populations of cancer stem cells (CSCs). The purpose of this study is to explore novel targets to regulate cancer stem cells and to test treatment option for Her2+ Trastuzumab-resistant breast cancer. Method: Trastuzumab resistance of Her2+ breast cancer cells (BT474) was induced by shRNA knockdown of PTEN and long term treatment of Trastuzumab (LTT) in comparison with Trastuzumab-sensitive BT474. The whole transcriptome RNA sequencing was performed and the differentially expressed genes were evaluated using dChip analyzer and the bioinformatics tool DAVID. Colony formation in soft agar and mammosphere formation were used to evaluate the effect of candidate genes on breast CSCs. Immunohistochemistry (IHC) was used to assess the protein expression levels in xenograft animal tissues and human breast cancer tissues. MTS assay was used to evaluate the effect of drug treatment to inhibit proliferation of BT474 and LTT. A xenograft model was used to determine whether drug efficacy to inhibit tumor formation. The secondary implantation was used to monitor cancer stem cells growth in vivo after treatment. Result: In comparison of BT474 and LTT under treatment of Sulforaphane (2-10 uM, 8-24 hr), RNA-Seq analysis revealed that 51 genes, including 23 up-regulated ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Biology Source Type: research