RT Journal Article SR Electronic T1 Survival of Human Multiple Myeloma Cells Is Dependent on MUC1 C-Terminal Transmembrane Subunit Oncoprotein Function JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 166 OP 174 DO 10.1124/mol.110.065011 VO 78 IS 2 A1 Li Yin A1 Rehan Ahmad A1 Michio Kosugi A1 Turner Kufe A1 Baldev Vasir A1 David Avigan A1 Surender Kharbanda A1 Donald Kufe YR 2010 UL http://molpharm.aspetjournals.org/content/78/2/166.abstract AB The MUC1 C-terminal transmembrane subunit (MUC1-C) oncoprotein is a direct activator of the canonical nuclear factor-κB (NF-κB) RelA/p65 pathway and is aberrantly expressed in human multiple myeloma cells. However, it is not known whether multiple myeloma cells are sensitive to the disruption of MUC1-C function for survival. The present studies demonstrate that peptide inhibitors of MUC1-C oligomerization block growth of human multiple myeloma cells in vitro. Inhibition of MUC1-C function also blocked the interaction between MUC1-C and NF-κB p65 and activation of the NF-κB pathway. In addition, inhibition of MUC1-C in multiple myeloma cells was associated with activation of the intrinsic apoptotic pathway and induction of late apoptosis/necrosis. Primary multiple myeloma cells, but not normal B-cells, were also sensitive to MUC1-C inhibition. Significantly, treatment of established U266 multiple myeloma xenografts growing in nude mice with a lead candidate MUC1-C inhibitor resulted in complete tumor regression and lack of recurrence. These findings indicate that multiple myeloma cells are dependent on intact MUC1-C function for constitutive activation of the canonical NF-κB pathway and for their growth and survival.