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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-3-22
pubmed:abstractText
The aim of this study was to examine whether Nedd4L (neural precursor cell expressed, developmentally down-regulated 4-like) participated in gallbladder carcinogenesis. We first immunohistochemically examined the expression of Nedd4L in various gallbladder tissue specimens. Weak immunoreactivity to Nedd4L-specific antibody was observed in normal or dysplastic epithelial cells. Cancer cells in non-invasive regions exhibited little immunoreactivity, whereas strong immunostaining was found in cytoplasm of many invasive cancers, especially at cancer invasive front with desmoplastic reaction. Notably, siRNA-mediated silencing of the Nedd4L gene significantly decreased the Matrigel-invasion activity and collagen invasion activity of cultured gallbladder cancer cells, without affecting the cell growth. The subtractive mRNA hybridization followed by RT-PCR and immunoblotting revealed that down-regulation of Nedd4L significantly decreased the expression of collagenases, matrix metalloproteinase (MMP)-1 and -13, in gallbladder cancer cells. Finally, immunohistochemical staining showed that many Nedd4L-expressing invasive gallbladder cancer cells co-expressed MMP-1 and MMP-13. These results indicated that over-expression of Nedd4L might lead to gallbladder cancer invasion by regulating the transcription of the MMP-1 and MMP-13 genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1365-2613
pubmed:author
pubmed:copyrightInfo
© 2010 The Authors. International Journal of Experimental Pathology © 2010 Blackwell Publishing Ltd.
pubmed:issnType
Electronic
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
79-86
pubmed:meshHeading
pubmed-meshheading:21039987-Adenocarcinoma, pubmed-meshheading:21039987-Aged, pubmed-meshheading:21039987-Cell Line, Tumor, pubmed-meshheading:21039987-Down-Regulation, pubmed-meshheading:21039987-Endosomal Sorting Complexes Required for Transport, pubmed-meshheading:21039987-Female, pubmed-meshheading:21039987-Gallbladder Neoplasms, pubmed-meshheading:21039987-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21039987-Gene Silencing, pubmed-meshheading:21039987-Humans, pubmed-meshheading:21039987-Immunohistochemistry, pubmed-meshheading:21039987-Male, pubmed-meshheading:21039987-Matrix Metalloproteinase 1, pubmed-meshheading:21039987-Matrix Metalloproteinase 13, pubmed-meshheading:21039987-Middle Aged, pubmed-meshheading:21039987-Neoplasm Invasiveness, pubmed-meshheading:21039987-RNA, Small Interfering, pubmed-meshheading:21039987-Transcription, Genetic, pubmed-meshheading:21039987-Transcriptional Activation, pubmed-meshheading:21039987-Ubiquitin-Protein Ligases
pubmed:year
2011
pubmed:articleTitle
Nedd4L modulates the transcription of metalloproteinase-1 and -13 genes to increase the invasive activity of gallbladder cancer.
pubmed:affiliation
Department of Pathology, Kochi Medical School, Nankoku, Japan. takeutit08@gmail.com
pubmed:publicationType
Journal Article