Ectopic expression of A-myb in transgenic mice causes follicular hyperplasia and enhanced B lymphocyte proliferation

被引:21
作者
DeRocco, SE
Iozzo, R
Ma, XP
Schwarting, R
Peterson, D
Calabretta, B
机构
[1] THOMAS JEFFERSON UNIV,KIMMEL CANC CTR,DEPT MICROBIOL & IMMUNOL,JEFFERSON MED COLL,PHILADELPHIA,PA 19107
[2] THOMAS JEFFERSON UNIV,DEPT PATHOL ANAT & CELL BIOL,JEFFERSON MED COLL,PHILADELPHIA,PA 19107
关键词
D O I
10.1073/pnas.94.7.3240
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The A-myb gene is a transcription factor that shares structural and functional similarities with the v-myb oncogene, To date, v-myb is the only myb gene directly implicated in tumorigenesis, a property attributed to its transactivating ability. Recent studies have demonstrated that A-myb, like v-myb, is a potent transcriptional activator, raising the possibility that A-myb may also participate in oncogenesis. To test this hypothesis, we generated fusion constructs that contained the human A-myb cDNA under control of the mouse metallothionein promoter and the mouse mammary tumor virus long terminal repeat, These constructs were Inserted into the germ line of mice, and the functional consequences of ectopic A-myb expression were examined. Although transgene expression was detected in a wide range of tissues, abnormalities were confined primarily to hematopoietic tissues, After a 9-month latency, A-myb transgenic mice developed hyperplasia of the spleen and lymph nodes, Enlarged tissues contained a polyclonally expanded B lymphocyte population that expressed a germinal center-cell phenotype. Transgenic B lymphocytes showed increased DNA synthesis in response to low dose mitogen stimulation, suggesting that A-myb may contribute to hyperplasia by increasing the rate of B cell proliferation.
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页码:3240 / 3244
页数:5
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