Study of a novel brain relatively specific gene LRRC4 involved in glioma tumorigenesis suppression using the Tet-on system.
LRRC4 is a novel relatively specific gene, which displays significant down-regulation in primary brain tumor biopsies and has the potential to suppress brain tumor growth. In this study, we investigated the growth inhibitory effect of LRRC4 on tumorigencity in vivo and on cell proliferation in vitro by a tetracycline-inducible expression system. Results showed that LRRC4 significantly reduced the growth and malignant grade of xenografts arising from glioblastoma U251MG cells. Cell proliferation was markedly inhibited after U251MG Tet-on-LRRC4 cell induction with doxycycline. Flow cytometry and Western blot analysis demonstrated that LRRC4 mediated a delay of the cell cycle in late G1, possibly through up-regulating the expressions of p21Waf1/cip1 and p27Kip1 and down-regulating the expressions of cyclin-dependent kinase 2, retinoblastoma protein and epidermal growth factor receptors. Together, these findings provide clues to the function of LRRC4 as a negative regulator of cell growth and underscore a link between the above-mentioned cyclins, cyclin-associated molecules and tumorigenicity.
Zhang
Qiu-Hong
QH
Cancer Research Institute, Central South University, Changsha 410078, China.
Wang
Li-Li
LL
Cao
Li
L
Peng
Cong
C
Li
Xiao-Ling
XL
Tang
Ke
K
Li
Wei-Fang
WF
Liao
Ping
P
Wang
Jie-Ru
JR
Li
Gui-Yuan
GY
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology; D014162:Transfection / Q000379:methods
D018797:Cell Cycle Proteins; C503331:LRRC4 protein, human; D009419:Nerve Tissue Proteins; D013752:Tetracycline