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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-2-7
pubmed:abstractText
Type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP9 are implicated in tumor invasion and metastasis. In patients with nasopharyngeal carcinoma (NPC), poor prognosis due to development of local and distant metastasis has been reported to be predicted by antibody titers against the Z protein which is an AP-1 family transcription factor encoded by the EBV BZLF1 immediate-early gene. Here we report that in patients with NPC, expression of Z in tumor cells correlates with advanced cervical lymph node metastasis which may suggest that Z affects tumor invasion and metastasis. We therefore tested if Z would induce expression of type IV collagenases. Transfection of Z expression plasmid into the C33A epithelial cell line increased expression of MMP9, but MMP2 expression was unaltered. Mutational analysis of the Z protein revealed that, in addition to all three functional domains of Z (dimerization domain, DNA binding domain, and activation domain), the carboxyl terminal 17 amino acids which stabilize the Z protein were necessary for induction of MMP9 expression. Analysis of the MMP9 promoter demonstrated that only AP-1 site close to the transcriptional start-site was essential for transactivation by Z. Previously we reported that Epstein-Barr virus latent membrane protein 1 (LMP1) stimulates MMP9 expression (Yoshizaki et al. Proc. Natl. Acad. Sci. 1998; 95: 3621-6). Thus, Z together with LMP1 may contribute to invasion and metastasis of NPC by inducing expression of MMP9.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0262-0898
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
431-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Matrix metalloproteinase 9 is induced by the Epstein-Barr virus BZLF1 transactivator.
pubmed:affiliation
Department of Otolaryngology, Cancer Research Institute, Kanazawa University, Japan. tomoy@med.kanazawa-u.ac.jp
pubmed:publicationType
Journal Article