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Constitutive activation of Stat5a by retrovirus integration in early pre-B lymphomas of SL/Kh strain mice
Tatsuaki Tsuruyama1, Takuro Nakamura, Guang Jin
1Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, 1 Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
We found that the second intron of Stat5a was one of the common integration sites of the endogenous ecotropic murine leukemia virus, i.e., SL/Kh virus integration-1 (Svi1), in early pre-B lymphomas in SL/Kh mice. The high expression of STAT5A induced by Svi1 integration and activation accelerated the transcription of its target genes such as c-Myc. Transfection of the constitutively active Stat5a mutant cDNA, but not of the wild-type cDNA, to the bone marrow cells induced colony formation of pre-B cells in a methylcellulose medium and escaped from dependence on IL-7. Such growth depended on a genetic factor in the SL/Kh strain. Consitutively high expression of Stat5a either by retrovirus integration or transfection of active mutant cDNA can be lymphomagenic to early pre-B cells in collaboration with a certain genetic background factor of mice.
We found that the second intron of Stat5a was one of the common integration sites of the endogenous ecotropic murine leukemia virus, i.e., SL/Kh virus integration-1 (Svi1), in early pre-B lymphomas in SL/Kh mice. The high expression of STAT5A induced by Svi1 integration and activation accelerated the transcription of its target genes such as c-Myc. Transfection of the constitutively active Stat5a mutant cDNA, but not of the wild-type cDNA, to the bone marrow cells induced colony formation of pre-B cells in a methylcellulose medium and escaped from dependence on IL-7. Such growth depended on a genetic factor in the SL/Kh strain. Consitutively high expression of Stat5a either by retrovirus integration or transfection of active mutant cDNA can be lymphomagenic to early pre-B cells in collaboration with a certain genetic background factor of mice.
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