title: RTVP-1 expression is regulated by SRF downstream of protein kinase C and contributes to the effect of SRF on glioma cell migration.
abstract: Gliomas are characterized by increased infiltration into the surrounding normal brain tissue. We recently reported that RTVP-1 is highly expressed in gliomas and plays a role in the migration of these cells, however the regulation of RTVP-1 expression in these cells is not yet described. In this study we examined the role of PKC in the regulation of RTVP-1 expression and found that PMA and overexpression of PKCα and PKCε increased the expression of RTVP-1, whereas PKCδ exerted an opposite effect. Using the MatInspector software, we identified a SRF binding site on the RTVP-1 promoter. Chromatin immunoprecipitation (ChIP) assay revealed that SRF binds to the RTVP-1 promoter in U87 cells, and that this binding was significantly increased in response to serum addition. Moreover, silencing of SRF blocked the induction of RTVP-1 expression in response to serum. We found that overexpression of PKCα and PKCε increased the activity of the RTVP-1 promoter and the binding of SRF to the promoter. In contrast, overexpression of PKCδ blocked the increase in RTVP-1 expression in response to serum and the inhibitory effect of PKCδ was abrogated in cells expressing a SRFT160A mutant. SRF regulated the migration of glioma cells and its effect was partially mediated by RTVP-1. We conclude that RTVP-1 is a PKC-regulated gene and that this regulation is at least partly mediated by SRF. Moreover, RTVP-1 plays a role in the effect of SRF on glioma cell migration.
authors.affiliation: The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Amotz
authors.initials: A
authors.lastname: Ziv-Av
authors.forename: Dvir
authors.initials: D
authors.lastname: Taller
authors.forename: Moshe
authors.initials: M
authors.lastname: Attia
authors.forename: Cunli
authors.initials: C
authors.lastname: Xiang
authors.forename: Hae Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Simona
authors.initials: S
authors.lastname: Cazacu
authors.forename: Susan
authors.initials: S
authors.lastname: Finniss
authors.forename: Gila
authors.initials: G
authors.lastname: Kazimirsky
authors.forename: Ronit
authors.initials: R
authors.lastname: Sarid
authors.forename: Chaya
authors.initials: C
authors.lastname: Brodie
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D005910:Glioma / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism*; D026362:Serum Response Factor / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: C094538:GLIPR1 protein, human; D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D026362:Serum Response Factor; D011493:Protein Kinase C