当前位置： SCI文献检索 > MOLECULAR PHARMACOLOGY期刊下所有文献 > Survival of human multiple myeloma cells is dependent on MUC1 C-terminal transmembrane subunit oncoprotein function.

Survival of human multiple myeloma cells is dependent on MUC1 C-terminal transmembrane subunit oncoprotein function.

Abstract：

:The MUC1 C-terminal transmembrane subunit (MUC1-C) oncoprotein is a direct activator of the canonical nuclear factor-kappaB (NF-kappaB) 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-kappaB p65 and activation of the NF-kappaB 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-kappaB pathway and for their growth and survival.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Yin L,Ahmad R,Kosugi M,Kufe T,Vasir B,Avigan D,Kharbanda S,Kufe D

doi

10.1124/mol.110.065011

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

166-74

issue

2

eissn

0026-895X

issn

1521-0111

pii

mol.110.065011

journal_volume

78

pub_type

杂志文章

相关文献

MOLECULAR PHARMACOLOGY文献大全