Document Detail

Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation.
MedLine Citation:
PMID:  11296287     Owner:  NLM     Status:  MEDLINE    
Jaagsiekte sheep retrovirus (JSRV) can induce rapid, multifocal lung cancer, but JSRV is a simple retrovirus having no known oncogenes. Here we show that the envelope (env) gene of JSRV has the unusual property that it can induce transformation in rat fibroblasts, and thus is likely to be responsible for oncogenesis in animals. Retrovirus entry into cells is mediated by Env interaction with particular cell-surface receptors, and we have used phenotypic screening of radiation hybrid cell lines to identify the candidate lung cancer tumor suppressor HYAL2/LUCA2 as the receptor for JSRV. HYAL2 was previously described as a lysosomal hyaluronidase, but we show that HYAL2 is actually a glycosylphosphatidylinositol (GPI)-anchored cell-surface protein. Furthermore, we could not detect hyaluronidase activity associated with or secreted by cells expressing HYAL2, whereas we could easily detect such activity from cells expressing the related serum hyaluronidase HYAL1. Although the function of HYAL2 is currently unknown, other GPI-anchored proteins are involved in signal transduction, and some mediate mitogenic responses, suggesting a potential role of HYAL2 in JSRV Env-mediated oncogenesis. Lung cancer induced by JSRV closely resembles human bronchiolo-alveolar carcinoma, a disease that is increasing in frequency and now accounts for approximately 25% of all lung cancer. The finding that JSRV env is oncogenic and the identification of HYAL2 as the JSRV receptor provide tools for further investigation of the mechanism of JSRV oncogenesis and its relationship to human bronchiolo-alveolar carcinoma.
S K Rai; F M Duh; V Vigdorovich; A Danilkovitch-Miagkova; M I Lerman; A D Miller
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Publication Detail:
Type:  Journal Article; 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:  98     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-04-11     Completed Date:  2001-05-10     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:  4443-8     Citation Subset:  IM    
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
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MeSH Terms
Carcinoma, Small Cell / pathology
Cell Transformation, Neoplastic*
Cell Transformation, Viral / physiology*
Genes, Tumor Suppressor*
Genes, env
Glycosylphosphatidylinositols / physiology*
Hyaluronoglucosaminidase / genetics,  metabolism*
Jaagsiekte sheep retrovirus / genetics,  physiology*
Lung Neoplasms / pathology
Membrane Fusion*
Phosphatidylinositol Diacylglycerol-Lyase
Tumor Cells, Cultured
Type C Phospholipases / metabolism
Grant Support
Reg. No./Substance:
0/Glycosylphosphatidylinositols; EC 3.1.4.-/Type C Phospholipases; EC; EC Diacylglycerol-Lyase
Comment In:
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4285-7   [PMID:  11296277 ]

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