Linked Life Data

17145867

Source:http://linkedlifedata.com/resource/pubmed/id/17145867

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2006-12-5
pubmed:abstractText
Tumor cells express HYAL1 hyaluronidase, which degrades hyaluronic acid. HYAL1 expression in bladder cancer cells promotes tumor growth, invasion, and angiogenesis. We previously described five alternatively spliced variants of HYAL1 that encode enzymatically inactive proteins. The HYAL1-v1 variant lacks a 30-amino acid sequence that is present in HYAL1. In this study, we examined whether HYAL1-v1 expression affects bladder cancer growth and invasion by stably transfecting HT1376 bladder cancer cells with a HYAL1-v1 cDNA construct. Although HYAL1-v1 transfectants expressed equivalent levels of enzymatically active HYAL1 protein when compared with vector transfectants, their conditioned medium had 4-fold less hyaluronidase activity due to a noncovalent complex formed between HYAL1 and HYAL1-v1 proteins. HYAL1-v1 transfectants grew 3- to 4-fold slower due to cell cycle arrest in the G(2)-M phase and increased apoptosis. In HYAL1-v1 transfectants, cyclin B1, cdc2/p34, and cdc25c levels were > or =2-fold lower than those in vector transfectants. The increased apoptosis in HYAL1-v1 transfectants was due to the extrinsic pathway involving Fas and Fas-associated death domain up-regulation, caspase-8 activation, and BID cleavage, leading to caspase-9 and caspase-3 activation and poly(ADP-ribose) polymerase cleavage. When implanted in athymic mice, HYAL1-v1-expressing tumors grew 3- to 4-fold slower and tumor weights at day 35 were 3- to 6-fold less than the vector tumors (P < 0.001). Whereas vector tumors were infiltrating and had high mitoses and microvessel density, HYAL1-v1 tumors were necrotic, infiltrated with neutrophils, and showed low mitoses and microvessel density. Therefore, HYAL-v1 expression may negatively regulate bladder tumor growth, infiltration, and angiogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11219-27
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17145867-Alternative Splicing, pubmed-meshheading:17145867-Animals, pubmed-meshheading:17145867-Apoptosis, pubmed-meshheading:17145867-Caspases, pubmed-meshheading:17145867-Cell Cycle, pubmed-meshheading:17145867-Cell Cycle Proteins, pubmed-meshheading:17145867-Cell Line, Tumor, pubmed-meshheading:17145867-Cell Movement, pubmed-meshheading:17145867-Cell Proliferation, pubmed-meshheading:17145867-Gene Expression, pubmed-meshheading:17145867-Gene Therapy, pubmed-meshheading:17145867-Humans, pubmed-meshheading:17145867-Hyaluronoglucosaminidase, pubmed-meshheading:17145867-Immunoblotting, pubmed-meshheading:17145867-Isoenzymes, pubmed-meshheading:17145867-Mice, pubmed-meshheading:17145867-Mice, Nude, pubmed-meshheading:17145867-Neovascularization, Pathologic, pubmed-meshheading:17145867-Poly(ADP-ribose) Polymerases, pubmed-meshheading:17145867-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17145867-Time Factors, pubmed-meshheading:17145867-Transfection, pubmed-meshheading:17145867-Urinary Bladder Neoplasms, pubmed-meshheading:17145867-Xenograft Model Antitumor Assays
pubmed:year
2006
pubmed:articleTitle
HYAL1-v1, an alternatively spliced variant of HYAL1 hyaluronidase: a negative regulator of bladder cancer.
pubmed:affiliation
Department of Urology, University of Miami Miller School of Medicine, Miami, Florida 33101, USA. vlokeshw@med.miami.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural