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A splice variant of CD99 increases motility and MMP-9 expression of human breast cancer cells through the AKT-, ERK-, and JNK-dependent AP-1 activation signaling pathways

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dc.contributor.authorByun, H. J.-
dc.contributor.authorHong, I. K.-
dc.contributor.authorKim, E.-
dc.contributor.authorJin, Y. J.-
dc.contributor.authorJeoung, D. I.-
dc.contributor.authorHahn, J. H.-
dc.contributor.authorKim, Y. M.-
dc.contributor.authorPark, S. H.-
dc.contributor.authorLee, H.-
dc.date.accessioned2009-10-06T03:04:20Z-
dc.date.available2009-10-06T03:04:20Z-
dc.date.issued2006-09-21-
dc.identifier.citationJ. Biol. Chem. 281, 34833-34847en
dc.identifier.issn0021-9258-
dc.identifier.urihttps://hdl.handle.net/10371/10185-
dc.description.abstractThe CD99 gene encodes two distinct transmembrane proteins by alternative splicing of its transcript. To examine the effects of two CD99 isoforms on the invasive phenotypes of breast cancer cells, MDA-MB-231 and MCF-7 human breast cancer cell lines were stably transfected with CD99 cDNAs encoding the major wild-type form (type I) or a minor splice variant (type II). As a result, expression of CD99 type II, but not type I, markedly elevated the motility, binding to fibronectin, MMP-9 expression, and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. In MDA-MB-435 breast cancer cells expressing both CD99 type I and type II, invasion-related cellular activities were inhibited by the transfection of small interfering RNA (siRNA) targeted to CD99 type II. Meanwhile, CD99 type II-induced MMP-9 expression in MDA-MB-231 cells was shown to be mediated by the binding of AP-1 factors to the MMP-9 gene promoter. Gel shift assay revealed that ligation of CD99 type II with antibody resulted in the binding of JunD to the AP-1 site of the MMP-9 promoter region. Initiation of CD99 type II signaling by antibody ligation increased expression of JunD and FosB AP-1 factors, along with phosphorylation of Src, Akt, p38 MAPK, ERK, and JNK. Knockdown of JunD and FosB by siRNA transfection abolished the positive effects of CD99 type II on the motility and MMP-9 expression of MDA-MB-231 cells. Increased expression of JunD and FosB as well as elevated cell motility and MMP-9 expression by CD99 type II ligation were also abrogated by inhibitors, dominant-negative forms, and siRNAs for Akt1, ERK1/2, and JNK1 but not for p38 MAPK. These results suggest that expression of a splice variant of CD99 contributes to the invasive ability of human breast cancer cells by up-regulating AP-1-mediated gene expression through the Akt-dependent ERK and JNK signaling pathways.en
dc.description.sponsorshipThis work was supported by a Vascular System Research Center grant from
the Korean Science and Engineering Foundation, South Korea.
en
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.subjectAlternative Splicingen
dc.subjectAntigens, CD/genetics/*metabolismen
dc.subjectBreast Neoplasms/enzymology/*metabolism/pathologyen
dc.subjectCell Adhesion Molecules/genetics/*metabolismen
dc.subjectCell Line, Tumoren
dc.subject*Cell Movementen
dc.subjectExtracellular Signal-Regulated MAP Kinases/*metabolismen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectHumansen
dc.subjectJNK Mitogen-Activated Protein Kinases/*metabolismen
dc.subjectMatrix Metalloproteinase 9/*metabolismen
dc.subjectProtein Isoforms/genetics/metabolismen
dc.subjectProto-Oncogene Proteins c-akt/*metabolismen
dc.subjectRNA Interferenceen
dc.subjectRNA, Small Interferingen
dc.subjectSignal Transductionen
dc.subjectTranscription Factor AP-1/*metabolismen
dc.titleA splice variant of CD99 increases motility and MMP-9 expression of human breast cancer cells through the AKT-, ERK-, and JNK-dependent AP-1 activation signaling pathwaysen
dc.typeArticleen
dc.contributor.AlternativeAuthor변희정-
dc.contributor.AlternativeAuthor홍인기-
dc.contributor.AlternativeAuthor김은숙-
dc.contributor.AlternativeAuthor진영준-
dc.contributor.AlternativeAuthor정두일-
dc.contributor.AlternativeAuthor한장희-
dc.contributor.AlternativeAuthor김영명-
dc.contributor.AlternativeAuthor박성회-
dc.contributor.AlternativeAuthor이한수-
dc.identifier.doi10.1074/jbc.M605483200-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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