Data from BMS-536924 Reverses IGF-IR-Induced Transformation of Mammary Epithelial Cells and Causes Growth Inhibition and Polarization of MCF7 Cells

• DOI: 10.1158/1078-0432.c.6517204.v1
• Publication Date: 2023-04-01T08:19:52Z
• Authors: Beate C. Litzenbu...; Hyun-Jung Kim; Isere Kuiatse; Joan M. Carboni; Ricardo M. Attar; Marco M. Gottardis; Craig R. Fairchild; Adrian V. Lee
• Keywords: Growth inhibition

<div>Abstract<p><b>Purpose:</b> This study aimed to test the ability of a new insulin-like growth factor receptor (<i>IGF-IR</i>) tyrosine kinase inhibitor, BMS-536924, reverse constitutively active <i>IGF-IR</i> (<i>CD8-IGF-IR</i>) transform MCF10A cells, and examine effect inhibitor on range human breast cancer cell lines.</p><p><b>Experimental Design:</b><i>CD8-IGF-IR</i>-MCF10A cells were grown in monolayer culture, three-dimensional (3D) as xenografts, treated with BMS-536924. Proliferation, cycle, polarity, apoptosis measured. Twenty-three lines culture viability was MCF7, MDA-MB-231, MDA-MB-435 BMS-536924 3D proliferation, migration, measured.</p><p><b>Results:</b> Treatment <i>CD8-IGF-IR</i>-MCF10A caused blockade restoration apical-basal enhanced apoptosis, resulting partial phenotypic reversion normal acini. In induced dose-dependent inhibition an accumulation G<sub>0</sub>/G<sub>1,</sub>, completely blocked <i>CD8-IGF-IR</i>–induced invasion, anchorage-independent growth. xenografts (100 mg/kg/day) showed 76% reduction xenograft volume. series 23 lines, inhibited proliferation 16 lines. Most strikingly, treatment MCF7 resulted formation hollow polarized lumen.</p><p><b>Conclusions:</b> These results show that small molecule is effective <i>IGF-IR</i>, causing <i>IGF-IR</i>–mediated transformed phenotype.</p></div>