期刊
GENES & DEVELOPMENT
卷 18, 期 21, 页码 2608-2613出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1243904
关键词
alveolar rhabdomyosarcoma; Pax3 : Fkhr; Pax7; FoxO1A; chromosomal translocation; satellite cell
资金
- NCI NIH HHS [K08 CA090438, 1K08 CA90438-01] Funding Source: Medline
To investigate the role of the translocation-associated gene Pax3.Fkhr in alveolar rhabdomyosarcomas, we generated a Cre-mediated conditional knock-in of Pax3:Fkhr into the mouse Pax3 locus. Exploring embryonic tumor cell origins, we replaced a Pax3 allele with Pax3.Fkhr throughout its expression domain, causing dominant-negative effects on Pax3 and paradoxical activation of the Pax3 target gene, c-Met. Ectopic neuroprogenitor cell proliferation also occurs. In contrast, activation later in embryogenesis in cells that express Pax7 results in viable animals with a postnatal growth defect and a moderately decreased Pax7+ muscle satellite cell pool, phenocopying Pax7 deficiency but remarkably not leading to tumors.
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