Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-1-24
pubmed:abstractText
Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the ErbB receptor ligand family, exists in distinct molecular forms with disparate biological activities. Previous studies have shown that the HB-EGF precursor, proHB-EGF, localizes to the cytoplasm of transitional cells of the human bladder urothelium and that the soluble form of the growth factor is an autocrine urothelial cell mitogen. In this study, we identify a potential role for proHB-EGF in transitional cell carcinoma (TCC) of the bladder. In an analysis of 33 TCC specimens and 8 normal controls, proHB-EGF, identified using an antibody directed against the cytoplasmic tail domain, localized to cell nuclei in a manner that correlated positively with tumor stage and grade (P < 0.001). The ability of proHB-EGF to localize to the nucleus was independently confirmed in a TCC cell line (TCCSUP), in which approximately 40% of transfected proHB-EGF was found to reside in the nuclear compartment. In Kaplan-Meier survival analysis, TCC patients with >20% proHB-EGF-positive cell nuclei demonstrated markedly reduced survival compared with patients with <20% proHB-EGF-positive nuclei (P < 0.005, log-rank test). In multivariate analysis, nuclear localization of proHB-EGF of >20% was an independent prognostic indicator of disease-specific mortality. This is the first report in any cell type that HB-EGF is capable of translocating to the cell nucleus. In addition, our findings suggest that nuclear proHB-EGF may play a role in disease progression in bladder cancer and possibly other cancers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
484-90
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
A nuclear form of the heparin-binding epidermal growth factor-like growth factor precursor is a feature of aggressive transitional cell carcinoma.
pubmed:affiliation
Departments of Urology and Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't