Expression and functional characterization of LRRC4, a novel brain-specific member of the LRR superfamily.
LRRC4, a novel member of LRR superfamily thought to be involved in development and tumorigenesis of the nervous tissue, has the potential to suppress tumorigenesis and cell proliferation of U251MG cells. This study aimed at revealing the correlation between expression of LRRC4 and the maintenance of normal function and tumorigenesis suppression within the central nervous system. We systematically analyzed the expression and tissue distributions of the gene in tissues. Results showed that LRRC4 expression was limited to normal adult brain, both in human and in mouse, and exhibited a development-regulated pattern, but was down-regulated in brain tumor tissues and U251MG cell line. Furthermore, dynamic alterations in gene expression associated with cell cycle progression were investigated by using Tet-on system. Results showed that LRRC4 induced a cell cycle delay at the late G1 phase, probably through the alteration of the expression of different cell cycle regulating proteins responsible for mediating G1-S progression, such as p21(Waf1/Cip1) and p27(Kip1), Cdk2 and PCNA, p-ERK1/2. These findings suggest that LRRC4 may play an important role in maintaining normal function and suppressing tumorigenesis in the central nervous system.
Zhang
Qiuhong
Q
Cancer Research Institute, Central South University, Changsha 410078, Hunan, People's Republic of China.
Wang
Jieru
J
Fan
Songqing
S
Wang
Lili
L
Cao
Li
L
Tang
Ke
K
Peng
Cong
C
Li
Zheng
Z
Li
Weifang
W
Gan
Kai
K
Liu
Zhongqi
Z
Li
Xiaoling
X
Shen
Shourong
S
Li
Guiyuan
G
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000235:genetics; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D015536:Down-Regulation; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014018:Tissue Distribution
C503331:LRRC4 protein, human; C503332:LRRC4 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger