Related to testes-specific, vespid, and pathogenesis protein-1 (RTVP-1) is overexpressed in gliomas and regulates the growth, survival, and invasion of glioma cells.
In this study, we examined the expression and functions of related to testes-specific, vespid, and pathogenesis protein 1 (RTVP-1) in glioma cells. RTVP-1 was expressed in high levels in glioblastomas, whereas its expression in low-grade astrocytomas and normal brains was very low. Transfection of glioma cells with small interfering RNAs targeting RTVP-1 decreased cell proliferation in all the cell lines examined and induced cell apoptosis in some of them. Overexpression of RTVP-1 increased astrocyte and glioma cell proliferation and the anchorage-independent growth of the cells. In addition, overexpression of RTVP-1 rendered glioma cells more resistant to the apoptotic effect of tumor necrosis factor-related apoptosis-inducing ligand and serum deprivation. To delineate the molecular mechanisms involved in the survival effects of RTVP-1, we examined the expression and phosphorylation of various apoptosis-related proteins. We found that overexpression of RTVP-1 decreased the phosphorylation of c-Jun-NH2-kinase and increased the expression of Bcl2 and that the protective effect of RTVP-1 was partially mediated by Bcl2. Finally, we found that RTVP-1 regulated the invasion of glioma cells as was evident by their enhanced migration through Matrigel and by their increased invasion in a spheroid confrontation assay. The increased invasive potential of the RTVP-1 overexpressors was also shown by the increased activity of matrix metalloproteinase 2 in these cells. Our results suggest that the expression of RTVP-1 is correlated with the degree of malignancy of astrocytic tumors and that RTVP-1 is involved in the regulation of the growth, survival, and invasion of glioma cells. Collectively, these findings suggest that RTVP-1 is a potential therapeutic target in gliomas.
Rosenzweig
Tovit
T
Gonda (Goldschmied) Medical Diagnosis Research Center, Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Ziv-Av
Amotz
A
Xiang
Cunli
C
Lu
Wei
W
Cazacu
Simona
S
Taler
Dvir
D
Miller
Cathie G
CG
Reich
Reuven
R
Shoshan
Yigal
Y
Anikster
Yair
Y
Kazimirsky
Gila
G
Sarid
Ronit
R
Brodie
Chaya
C
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology; D001254:Astrocytoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*
C094538:GLIPR1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D020778:Matrix Metalloproteinase 2