Document Detail

Heparin-binding epidermal growth factor-like growth factor, a v-Jun target gene, induces oncogenic transformation.
MedLine Citation:
PMID:  10318950     Owner:  NLM     Status:  MEDLINE    
Jun is a transcription factor belonging to the activator protein 1 family. A mutated version of Jun (v-Jun) transduced by the avian retrovirus ASV17 induces oncogenic transformation in avian cell cultures and sarcomas in young galliform birds. The oncogenicity of Jun probably results from transcriptional deregulation of v-Jun-responsive target genes. Here we describe the identification and characterization of a growth-related v-Jun target, a homolog of heparin-binding epidermal growth factor-like growth factor (HB-EGF). HB-EGF is strongly expressed in chicken embryo fibroblasts (CEF) transformed by v-Jun. HB-EGF expression is not detectable or is marginal in nontransformed CEF. Using a hormone-inducible Jun-estrogen receptor chimera, we found that HB-EGF expression is correlated with v-Jun activity. In this system, induction of v-Jun is followed within 1 hr by elevated levels of HB-EGF. In CEF infected with various Jun mutants, HB-EGF expression is correlated with the oncogenic potency of the mutant. Constitutive expression of HB-EGF conveys to CEF the ability to grow in soft agar and to form multilayered foci of transformed cells on a solid substrate. These observations suggest that HB-EGF is an effector of Jun-induced oncogenic transformation.
S l Fu; I Bottoli; M Goller; P K Vogt
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  96     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-06-17     Completed Date:  1999-06-17     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5716-21     Citation Subset:  IM    
Department of Molecular and Experimental Medicine, The Scripps Research Institute, BCC 239, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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MeSH Terms
Amino Acid Sequence
Cell Division
Cell Transformation, Neoplastic / genetics*
Cells, Cultured
Chick Embryo
Cloning, Molecular
Epidermal Growth Factor / genetics*,  metabolism
Gene Expression Regulation, Neoplastic / genetics
Intercellular Signaling Peptides and Proteins
Molecular Sequence Data
Oncogene Protein p65(gag-jun) / genetics*,  metabolism
Oncogenes / genetics
RNA, Messenger / metabolism
Receptors, Estrogen / genetics
Recombinant Fusion Proteins / genetics
Sequence Alignment
Grant Support
Reg. No./Substance:
0/Intercellular Signaling Peptides and Proteins; 0/Oncogene Protein p65(gag-jun); 0/RNA, Messenger; 0/Receptors, Estrogen; 0/Recombinant Fusion Proteins; 149176-25-0/heparin-binding EGF-like growth factor; 62229-50-9/Epidermal Growth Factor

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