decreased autocrine egfr signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad减少自分泌表皮生长因子受体信号在骨转移性乳腺癌细胞抑制肿瘤的生长和乳腺脂肪垫.pdfVIP

Decreased Autocrine EGFR Signaling in Metastatic Breast Cancer Cells Inhibits Tumor Growth in Bone and Mammary Fat Pad 1 2,3 1 1 4,5 Nicole K. Nickerson , Khalid S. Mohammad , Jennifer L. Gilmore , Erin Crismore , Angela Bruzzaniti , Theresa A. Guise2,3, John Foley1,3,5,6* 1 Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana, United States of America, 2 Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, 3 Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, 4 Department of Oral Biology, Indiana University School of Dentistry, Indianapolis, Indiana, United States of America, 5 Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, 6 Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America Abstract Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRN