Retroviral transduction of T-cell antigen receptor β-chain and myc genes

Abstract

Support for multistage models of oncogenesis has been provided by several highly leukaemogenic retrovirus isolates that have transduced more than one host cell gene. Where functional studies have been performed, these retroviral oncogenes show synergy for in vitro transformation and leukaemogenesis. In naturally occurring feline leukaemias associated with feline leukaemia virus (FeLV), retroviral transduction of myc is a frequent oncogenic mechanism. But evidence suggesting that the FeLV v-myc genes might be insufficient for leukaemogenesis was provided by the latency (12 weeks) and clonality of FeLV/v-myc-induced tumours and the absence of demonstrable in vitro transformation by these viruses. In the search for secondary leukaemogenic events in FeLV/v-myc tumours, we have identified a case of FeLV transduction of a T-cell antigen receptor beta-chain gene. The proviruses carrying this gene (which we have named v-tcr) were a separate population from those carrying v-myc. In its normal role, the T-cell receptor beta-chain forms part of a multimeric complex involved in antigen recognition and T-cell activation. We suggest that v-tcr is a novel viral oncogene which assisted v-myc in the genesis of a naturally occurring case of thymic lymphosarcoma.

Proviral insertions induce the expression of bone-specific isoforms of PEBP2αA (CBFA1): Evidence for a new myc collaborating oncogene

“…Up-regulation of TCR͞CD3 expression is a critical event in T cell development (36), and transcriptional stimulation of the component genes might conceivably promote cell transit through growth͞ differentiation checkpoints or allow survival of cells carrying TCRs with suboptimal or excessive affinity for major histocompatibility complex. The collaboration of TCR complex signaling with Myc would also provide a parallel for our earlier observation of retroviral transduction of both c-myc and TCR-␤ in a naturally occurring T cell lymphoma (37) and could account for the highly consistent TCRϩCD3ϩ phenotype of CD2-myc lymphomas (8).…”

Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog

“…The probe DNA consisted of the virally transduced feline TCR b chain region obtained from a feline T17 genomic library (Fulton et al, 1987). A 390 bp restriction DNA fragment containing the TCR b chain was labelled using a 32 P-(dCTP) and the Prim-it random primer kit as per the manufacturers protocol (Stratagene).…”

Apparent bypass of negative selection in CD8+ tumours in CD2-myc transgenic mice

“…Further, Bahler and Levy (1992) have reported that there is evidence for antigen selection in the development of follicular lymphomas. Analysis of a thymic lymphoma associated with a field case of feline leukaemia virus (FeLV) infection revealed the presence of a provirus which had incorporated a fully processed TCR gene, raising the possibility that antigen stimulation or inappropriate antigen recognition may have been important in the genesis of this tumour (Fulton et al, 1987). Studies involving murine radiation leukaemia virus (RadLV) have shown that free virus particles can modulate the growth of a RadLV-induced T-cell lymphoma cell line (O'Neill, 1994) and that the VP repertoire of RadLV-induced lymphomas is restricted, indicating non-random selection (Sen-Majumdar et al, 1994 Acha-Orbea & Palmer, 1991;Simpson,-1992;Marrack et al, 1993;Simpson et al, 1993 transferred to nylon filters and hybridised to the appropriate radiolabelled probes at high stringency using the protocols described by Sambrook et al (1989).…”