GSBS Dissertations and Theses

Title

Characterization of a Deletion in erb [subscript erb]B Sequences Associated with Angiosarcoma: a Thesis

Approval Date

12-1-1998

Document Type

Doctoral Dissertation

Department

Graduate School of Biomedical Sciences, Department of Biochemistry and Molecular Biology

Subjects

Alpharetrovirus; Hemangioma; Academic Dissertations

Abstract

Analyses of 11 new erbB transducing viruses had previously correlated differences in disease potential with deletions or truncations in sequences encoding the carboxy-terminal domain of the chicken EGF receptor. erbB sequences of two of these viruses, one inducing only erythroblastosis (AEV-5005) and the other inducing only angiosarcoma (AAV-5005), were molecularly cloned. Sequence analysis confirmed the presence of an internal deletion in AAV-5005. The deletion was found to be inframe and to have removed 177 nucleotides. The deleted sequence had encoded a region between the kinase domain and the autophosphorylation sites of the EGF receptor. To establish that the deletion was responsible for the change in disease potential two recombinant viruses were constructed. One recombinant virus (srE) contained erbB sequences from AEV-5005. The other recombinant virus (srE/A) was identical to srE except that a restriction fragment from AAV-5005 which contained the deletion was substituted for the homologous fragment of AEV-5005. The srE virus induced only erythroblastosis, while the srE/A virus induced angiosarcoma as well as erythroblastosis. This demonstrated that the deletion was sufficient to induce angiosarcoma. Metabolic labelling did not reveal any difference in the expression or processing of these proteins and both became phosphorylated in an in vitro kinase assay. The biochemical basis for the difference in disease potential of these two related proteins remains to be determined.

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