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

Autor: Susan E. DeRocco, Xiao-Ping Ma, Roland Schwarting, Bruno Calabretta, Renato V. Iozzo, David S. Peterson
Jazyk: angličtina
Rok vydání: 1997
Předmět:
Popis: The A-mybgene is a transcription factor that shares structural and functional similarities with the v-myboncogene. To date, v-mybis the onlymybgene 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-mybmay also participate in oncogenesis. To test this hypothesis, we generated fusion constructs that contained the human A-mybcDNA 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-mybexpression 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-mybtransgenic 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-mybmay contribute to hyperplasia by increasing the rate of B cell proliferation.
Databáze: OpenAIRE