Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1998-4-8
pubmed:abstractText
Previously, we described cloning of three alternatively spliced mRNA forms of human FGF8, a, b, and e, of which the b form is the major expressed species in both normal and tumor prostatic epithelial cells. In this report, we describe construction and overexpression of sense and antisense sequences of either the full length FGF8b coding region (215-amino acids or 215aa), 103aa N-terminal part or a smaller N-terminal region (34aa), each including the 23aa putative signal peptide domain, via a retrovirus system. While the morphologic transforming activities of the sense 215aa and 103aa constructs were similar in NIH3T3 cells, 103aa displayed reduced soft agar clonogenic activity. The 34aa construct was practically inert in these assays, although its expression could mimic the ability of 215aa or 103aa in conferring cell growth under reduced serum condition. Overexpression of any of the three constructs in antisense orientation, however, was similarly effective in reversing the morphology and anchorage-independent growth property of FGF8b-transfected NIH3T3 cells. The expression of the antisense 215aa construct significantly reduced the growth rate of the human prostatic carcinoma DU145 cells and inhibited their soft agar clonogenic activity and in vivo tumorigenicity in nude mice. Taken together, these results identify N-terminal portions of FGF8 protein isoform for having the domains necessary for one or more of the biologic effects examined, and suggest that low levels of FGF8 expressed in prostatic epithelial cells may contribute significantly to their growth and tumorigenic properties.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1487-92
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Downregulation of human FGF8 activity by antisense constructs in murine fibroblastic and human prostatic carcinoma cell systems.
pubmed:affiliation
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't