In investigations of the mechanisms of regulation of the replication of equine infectious anemia virus (EIAV), cDNA libraries prepared from cells infected with EIAV were probed so as to isolate putative Rev-encoding cDNAs. Three structurally distinct variants generated by alternative splicing were identified. Two Rev proteins (18 and 16 kDa) were encoded by two cDNAs, while the third encoded only a 16 kDa species. The two Rev proteins were shown to potentiate the cytoplasmic expression of transcripts containing the env region of EIAV. This marks the first demonstration of EIAV rev gene function. Identification of the EIAV RRE (rev responsive element) is in progress. The lymphoproliferative disease virus (LPDV) of turkeys is acutely oncogenic, but determination of the complete nucleotide sequence of its genome died not reveal the presence of an oncogene. Protein sequence analysis of gag-pol gene products indicates that LPDV, although most closely related to avian oncoviruses, possesses a unique gag protein (p31) of unknown function and generates its protease by a distinct mechanism. A cDNA predicted to encode a transmembrane tyrosine kinase receptor with sequence features characteristic of known fibroblast growth factor (FGF) receptors was isolated from a human mammary epithelial cell and was subsequently shown to represent FGF receptor-4 (FGFR-4). FGFR-4 bound both acidic and basic FGF (Kd - 10-15 and 120 pM) but not keratinocyte growth factor (KGF). To determine whether FGF receptors contribute to the development of human tumors, screened RNAs were prepared from cell lines derived from a variety of solid tumors. High levels of the FGFR-4 transcript were specifically (relative to FGFR-1) and frequently detected in human mammary and kidney carcinomas, but only infrequently in other tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP004941-21
Application #
3774775
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code