AVIAN ERYTHROLEUKEMIA AND C-ERBB ACTIVATION

Project: Research project

Description

Avian leukosis virus (ALV) is the prototype of non-acute retroviruses, a
group of naturally occurring cancer viruses which do not carry oncogenes
and induce cancers by proviral insertional activation of host oncogenes.
In the previous grant period, we have established that ALV induces
erythroblastosis by insertional activation of the host oncogene c-erbB
which has recently been shown to be related, if not identical, to the EGF
receptor. We have identified several extraordinary features regarding
c-erbB activation; all the proviruses are inserted in the middle of the
erbB gene at a point very close to the exon where homology to v-erbB
starts, suggesting truncation of the protein at this point maybe important
for oncogenesis. The proviruses utilize their 5'LTR (rather than 3' LTR)
promoter to transcribe a readthrough message encompassing both the viral
genes and the downstream c-erbB sequences. This is followed by a novel
splicing scheme to generate the activated c-erbB transcript. The activated
c-erbB gene product contains the viral envelope signal sequence, the region
related to v-erbB and a 34 amino acid c-terminal domain homologous to
EGF-receptor which contains the major autophosphorylation site. These
findings provide new leads in our understanding of the viral oncogenesis
mechanisms, the oncogenic conversion of a normal cellular receptor gene,
and the role of a growth factor receptor in leukemgenesis. We wish to
extend these analyses to more clearly define (1) the structure of the
chicken c-erbB locus with an emphasis on its possible identity to the
EGF-receptor (2) the nature of the multiple transcripts of the normal and
activated c-erbB genes (3) the properties of the activated c-erbB protein
(4) the oncogenic determinants of the c-erbB (or EGF receptor) gene and (5)
the mechanisms involved in the transduction of activated c-erbB to generate
an acute oncogenic retrovirus.
StatusFinished
Effective start/end date9/1/8412/31/05

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $258,834.00
  • National Institutes of Health: $276,962.00
  • National Institutes of Health: $311,099.00
  • National Institutes of Health
  • National Institutes of Health: $303,295.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $295,224.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $285,939.00
  • National Institutes of Health
  • National Institutes of Health: $288,098.00
  • National Institutes of Health
  • National Institutes of Health: $243,672.00

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Leukemia, Erythroblastic, Acute
Retroviridae
Oncogenes
erbB Genes
Phosphotransferases
Insertional Mutagenesis
Avian Leukosis Virus
Chickens
Epidermal Growth Factor Receptor
Proviruses
Protein-Tyrosine Kinases
Passive Cutaneous Anaphylaxis
ErbB-2 Receptor
Organized Financing
Oncogenic Viruses
Prostatic Neoplasms
Catalytic Domain
Genes
Interleukin-6 Receptors
Growth Factor Receptors

ASJC

  • Medicine(all)