Science Links Japan | VCP (p97) Regulates NF.KAPPA.B Signaling Pathway, Which Is Important for Metastasis of Osteosarcoma Cell Line.

VCP (p97) Regulates NF.KAPPA.B Signaling Pathway, Which Is Important for Metastasis of Osteosarcoma Cell Line.

Accession number;02A0357267

Title;VCP (p97) Regulates NF.KAPPA.B Signaling Pathway, Which Is Important for Metastasis of Osteosarcoma Cell Line.

Author; ASAI T (Osaka Univ. Graduate School Of Medicine, Osaka) TOMITA Y (Osaka Univ. Graduate School Of Medicine, Osaka) NAKATSUKA S (Osaka Univ. Graduate School Of Medicine, Osaka) HOSHIDA Y (Osaka Univ. Graduate School Of Medicine, Osaka) MYOUI A (Osaka Univ. Graduate School Of Medicine, Osaka) YOSHIKAWA H (Osaka Univ. Graduate School Of Medicine, Osaka) AOZASA K (Osaka Univ. Graduate School Of Medicine, Osaka)

Journal Title;Jpn J Cancer Res

Journal Code:F0633A

ISSN:0910-5050

VOL.93;NO.3;PAGE.296-304(2002)

Figure&Table&Reference;FIG.8, TBL.1, REF.42

Pub. Country;Japan

Language;English

Abstract;In order to identify genes associated with metastasis, suppression subtractive hybridization (SSH) was performed using murine osteosarcoma cell line Dunn and its subline with higher metastatic potential, LM8. SSH revealed expression of the gene encoding valosin-containing protein (VCP; also known as p97) to be constitutively activated in LM8 cells, but it declined in Dunn cells when the cells became confluent. Because VCP is known to be involved in the ubiquitination process of Inhibitor-.KAPPA.B.ALPHA. (I.KAPPA.B.ALPHA.), an inhibitor of nuclear factor-.KAPPA.B (NF.KAPPA.B), whether VCP influences NF.KAPPA.B activation or not was examined by using VCP-transfected Dunn cells (Dunn/VCPs). When stimulated with tumor necrosis factor-.ALPHA. (TNF.ALPHA.), Dunn/VCPs showed constantly activated NF.KAPPA.B, although in the original Dunn cells and control vector transfectant (Dunn/Dunn-c) NF.KAPPA.B activation ceased when the cells became confluent. Western immunoblot analysis showed an increase of phosphorylated I.KAPPA.B.ALPHA. (p-I.KAPPA.B.ALPHA.) in the cytoplasm of confluent Dunn/Dunn-c cells compared to that of Dunn/VCPs. Therefore, decrease of p-I.KAPPA.B.ALPHA. degrading activity might be responsible for the decrease in NF.KAPPA.B activation. In vitro apoptosis assay demonstrated increased apoptosis rates of Dunn/Dunn-c cells after TNF.ALPHA. stimulation compared to those of Dunn/VCPs and LM8 cells. In vivo metastasis assay showed increased incidences of metastatic events in Dunn/VCP-1 inoculated male C3H mice compared to those in Dunn/Dunn-c inoculated mice. These findings suggested that VCP expression plays an important role in the metastatic process. Anti-apoptotic potential in these cells owing to constant NF.KAPPA.B activation via efficient cytoplasmic p-I.KAPPA.B.ALPHA. degrading activity may explain the increased metastatic potential of these cells. (author abst.)

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