SCL, the gene implicated in human T-cell leukaemia, is oncogenic in a murine T-lymphocyte cell line.
SCL (TAL-1) is implicated in the generation of human T-cell acute lymphoblastic leukaemia. To directly examine the role of this putative oncogene, an SCL retrovirus was constructed and used to infect a v-ABL transformed T-lymphocyte cell line. Thirteen independent SCL-infected and four control cell lines were established and injected subcutaneously into syngeneic mice. Mice injected with SCL-infected clonal cell lines died significantly more rapidly than control animals. By day 200 46% (40/87) of animals injected with SCL-infected cell lines had died due to disseminated transplantable lymphoid tumours. In contrast only 22% of control mice were dead by day 200 (P < 0.0015). Of possible relevance to the enhanced tumourigenesis, some SCL-infected cell lines displayed increased clonogenicity in agar. Increased cell growth was even more striking when ex-vivo tumour-derived cell lines were studied. Thus, SCL can co-operate with v-ABL to hasten T-cell tumourigenesis. This is the first direct evidence demonstrating that SCL can behave as an oncogene.
Elwood
N J
NJ
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Cook
W D
WD
Metcalf
D
D
Begley
C G
CG
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics*; D016313:Genes, abl; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000209:etiology*; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes / Q000382:microbiology; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human