MUC4 Abrogation of Herceptin Responsiveness in Breast Cancer

摘要

Muc4 is a heterodimeric glycoprotein complex consisting of a peripheral mucin subunit tightly but noncovalently linked to a transmembrane subunit. Muc4 is overexpressed on a number of human breast tumors. Overexpression of Muc4 has been shown to block cell-cell and cell-matrix interactions, protect tumor cells from immune surveillance and promote metastasis. In addition, Muc4 has been shown to act as a ligand for ErbB2/HER2, the target of the therapeutic antibody Herceptin. Using A375 melanoma and MCF7 breast adenocarcinoma cells stably transfected with tetracycline regulatable Muc4, we have investigated whether its overexpression can repress antibody binding to cell surface-expressed ErbB2.