International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

B18. Abnormal Signal Transduction by Retrovirus Integration in Pre-B Lymphoma of SL/Kh Mice

Tatsuaki Tsuruyama1, Takuro Nakamura2, Guang Jin1, Hiai Hiroshi1
1Department of Pathology and Biology of Disease, Kyoto university, Graduate School of medicine, 2Cancer Institute

New somatic acquisition of proviral genome was observed with high frequency in the pre-B lymphoma-prone inbred strain mouse SL/Kh. We cloned one of the common viral integration sites by inverse PCR method and named it Svi1. This integartion was observed in 5% of lymphoma samples within about 500bp range in the second exon of signal transducer and transcription activator 5a (Stat5a) gene, which is upstream of protein coding region. In all cases with Svi1, high expression of Stat5a mRNA and protein was observed. Furthermore, activated Stat5a protein with phosphorylated Tyr694 was detected from nuclear extract and gel shift assay showed its DNA binding ability by the probe containing GAS element. From these results, we thought that acquisition of autonomous proliferation ability by the transcriptional activation of other transcription factors, cytokines and protein kinases by high expression of Stat5a is important for pre-B lymphomagenesis.

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