RGS2 Suppresses Breast Cancer Cell Growth via a MCPIP1-Dependent Pathway

Title
RGS2 Suppresses Breast Cancer Cell Growth via a MCPIP1-Dependent Pathway
Author(s)
백석환류지효[류지효]박대원황빈강수환이수정이추희배외식[배외식]이진구[이진구]
Keywords
PROTEIN SIGNALING 2; END RULE PATHWAY; MESSENGER-RNA; REGULATOR; EXPRESSION; DEGRADATION; ACTIVATION; PHOSPHORYLATION; RESISTANCE; APOPTOSIS
Issue Date
201502
Publisher
WILEY-BLACKWELL
Citation
JOURNAL OF CELLULAR BIOCHEMISTRY, v.116, no.2, pp.260 - 267
Abstract
Regulator of G protein signaling 2 (RGS2) is a member of a family of proteins that functions as a GTPase-activating protein (GAP) for G alpha subunits. RGS2 mRNA expression is lower in breast cancerous tissues than in normal tissues. In addition, expression of RGS2 is also lower in MCF7 (cancerous breast cells) than in MCF10A (normal breast cells). Here we investigated whether RGS2 inhibits growth of breast cancer cells. RGS2 overexpression in MCF7 cells inhibited epidermal growth factor- or serum-induced proliferation. In HEK293T cells expressing RGS2, cell growth was also significantly suppressed (In addition, exogenous expression of RGS2 in HEK293T cells resulted in the significant suppression of cell growth). These results suggest that RGS2 may have a tumor suppressor function. MG-132 treatment of MCF7 cells increased endogenous or exogenous RGS2 levels, suggesting a post-transcriptional regulatory mechanism that controls RGS2 protein levels. RGS2 protein was degraded polyubiquitinated the K71 residue, but stabilized by deubiquitinase monocyte chemotactic protein-induced protein 1 (MCPIP1), and not affected by dominant negative mutant (C157A) of MCPIP1. Gene expression profiling study showed that overexpression of RGS2 decreased levels of testis specific Y encoded like protein 5 (TSPYL5), which plays a causal role in breast oncogenesis. TSPYL5 protein expression was low in MCF10A and high in MCF7 cells, showing the opposite aspect to RGS2 expression. Additionally, RGS2 or MCPIP1 overexpression in MCF7 cells decreased TSPYL5 protein level, indicating that RGS2 stabilized by MCPIP1 have diminished TSPYL5 protein levels, thereby exerting an inhibitory effect of breast cancer cell growth. (C) 2014 Wiley Periodicals, Inc.
URI
http://hdl.handle.net/YU.REPOSITORY/33530http://dx.doi.org/10.1002/jcb.24964
ISSN
0730-2312
Appears in Collections:
의과대학 > 생화학.분자생물학교실 > Articles
의과대학 > 성형외과학교실 > Articles
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