BCL6 cooperates with CD40 stimulation and loss of p53 function to rapidly transform primary B cells.
BCL6 cooperates with CD40 stimulation and loss of p53 function to rapidly transform primary B cells.
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DOI：
10.1002/ijc.24450
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发表时间：
2009-08-15
影响因子：
6.4
通讯作者：
Dent A
中科院分区：
文献类型：
--
作者：
Kusam S;Munugalavadla V;Sawant D;Dent A
The BCL6 transcriptional repressor protein has been shown to promote B cell lymphoma in transgenic mouse models. The mechanism by which BCL6 transforms primary B cells is unclear, although repression of the p53 tumor suppressor is thought to play a role. Here we show that BCL6 has critical oncogene functions that are independent of p53 repression. We find BCL6 cooperates with constitutive CD40 signaling to rapidly transform p53-deficient primary mouse B cells in vitro. Constitutive CD40 signaling alone does not transform p53-deficient B cells, indicating that BCL6 acts specifically as an immortalizing oncogene in this system. The BCL6 transformed B cells are polyclonal and form polyclonal tumors. At the initiation of the cultures, BCL6 does not significantly alter cell cycle progression, but does promote increased cell survival. Early cultures of BCL6 expressing B cells show marked repression of ATR and p27kip1 but not other BCL6 target genes, suggesting that the ATR and p27kip1 genes have key early roles in mediating BCL6 transformation function. BCL6 transformed cell lines show further decreases of ATR and p27kip1 expression plus strong decreases in Blimp1 and PDCD2 expression. This study provides important clues about the critical target genes used by BCL6 to transform primary B cells and indicates that the CD40 signaling pathway can collaborate with BCL6 in the transformation of primary B cells. Lastly, our study demonstrates a rapid in vitro system to analyze the transformation function of BCL6.
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DOI：
10.1084/jem.192.12.1841
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Fearon DT
影响因子：
32.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Lasky, LA
影响因子：
32.4
作者：
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通讯作者：
Staudt, LM
DOI：
10.1073/pnas.0406138101
发表时间：
2004-09-28
影响因子：
11.1
作者：
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通讯作者：
Baron, JM