Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26907633
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26907633
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Blood
2016 ; 127
(21
): 2587-97
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
MUC1-C drives MYC in multiple myeloma
#MMPMID26907633
Tagde A
; Rajabi H
; Bouillez A
; Alam M
; Gali R
; Bailey S
; Tai YT
; Hideshima T
; Anderson K
; Avigan D
; Kufe D
Blood
2016[May]; 127
(21
): 2587-97
PMID26907633
show ga
Multiple myeloma (MM) cell lines and primary tumor cells are addicted to the MYC
oncoprotein for survival. Little is known, however, about how MYC expression is
upregulated in MM cells. The mucin 1 C-terminal subunit (MUC1-C) is an oncogenic
transmembrane protein that is aberrantly expressed in MM cell lines and primary
tumor samples. The present studies demonstrate that targeting MUC1-C with
silencing by clustered regularly interspaced short palindromic repeat
(CRISPR)/CRISPR-associated protein 9 editing or with the GO-203 inhibitor is
associated with downregulation of MYC messenger RNA and protein. The results show
that MUC1-C occupies the MYC promoter and thereby activates the MYC gene by a
?-catenin/transcription factor 4 (TCF4)-mediated mechanism. In this way, MUC1-C
(1) increases ?-catenin occupancy on the MYC promoter, (2) forms a complex with
?-catenin and TCF4, and, in turn, (3) drives MYC transcription. Analysis of MM
cells using quantitative real-time reverse transcription polymerase chain
reaction arrays further demonstrated that silencing MUC1-C is associated with
downregulation of MYC target genes, including CCND2, hTERT, and GCLC Analysis of
microarray data sets further demonstrated that MUC1 levels positively correlate
with MYC expression in MM progression and in primary cells from over 800 MM
patients. These findings collectively provide convincing evidence that MUC1-C
drives MYC expression in MM.
free
free
free
