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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Cancer+Res
2015 ; 5
(10
): 3210-20
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Tumor suppressor SPOP mediates the proteasomal degradation of progesterone
receptors (PRs) in breast cancer cells
#MMPMID26693071
Gao K
; Jin X
; Tang Y
; Ma J
; Peng J
; Yu L
; Zhang P
; Wang C
Am J Cancer Res
2015[]; 5
(10
): 3210-20
PMID26693071
show ga
Progesterone induces proliferation of breast cancer cells and contributes to the
development of breast cancer. The effects of progesterone are mediated by
progesterone receptors (PRs). However, it is still not fully understood how the
proliferative effects of PR is regulated in vivo. Increasing amount of evidence
strongly suggests that dysregulation of ubiquitin-proteasome system is closely
associated with cancer pathogenesis. Speckle-type POZ protein (SPOP) is an
adaptor protein of the CUL3-based E3 ubiquitin ligase complexes. SPOP represents
one of the highest loci for loss of heterozygosity (LOH) in breast cancer. SPOP
downregulation contributes to breast cancer cell growth and invasion. In this
study, we revealed PR as a bona fide substrate for SPOP. SPOP interacts with PR
in vivo and targets PR for ubiquitin-dependent proteasomal degradation. Moreover,
SPOP suppresses progesteroneinduced PR transactivation, S phase entry, and Erk1/2
activation. Our study revealed novel molecular mechanisms underlying the
regulation of PR protein homeostasis in breast cancer cells, and provided
insights in understanding the relationship between SPOP inactivation and the
development of breast cancer.