|
|
|
|
Cell-Cycle Dependent Expression of a Translocation-Mediated Fusion Oncogene Mediates Checkpoint Adaptation in Rhabdomyosarcoma
|
|
|
|
|
|
|
|
نویسنده
|
kikuchi k. ,hettmer s. ,aslam m.i. ,michalek j.e. ,laub w. ,wilky b.a. ,loeb d.m. ,rubin b.p. ,wagers a.j. ,keller c.
|
|
منبع
|
plos genetics - 2014 - دوره : 10 - شماره : 1
|
|
چکیده
|
Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in childhood. most rhabdomyosarcoma falls into one of two biologically distinct subgroups represented by alveolar or embryonal histology. the alveolar subtype harbors a translocation-mediated pax3:foxo1a fusion gene and has an extremely poor prognosis. however,tumor cells have heterogeneous expression for the fusion gene. using a conditional genetic mouse model as well as human tumor cell lines,we show that that pax3:foxo1a expression is enriched in g2 and triggers a transcriptional program conducive to checkpoint adaptation under stress conditions such as irradiation in vitro and in vivo. pax3:foxo1a also tolerizes tumor cells to clinically-established chemotherapy agents and emerging molecularly-targeted agents. thus,the surprisingly dynamic regulation of the pax3:foxo1a locus is a paradigm that has important implications for the way in which oncogenes are modeled in cancer cells. © 2014 kikuchi et al.
|
|
|
|
|
آدرس
|
pediatric cancer biology program,papé family pediatric research institute,department of pediatrics,oregon health and science university,portland,or, United States, the howard hughes medical institute and department of stem cell and regenerative biology,harvard university,cambridge,ma,united states,department of pediatric oncology,dana farber cancer institute and division of pediatric hematology/oncology,children's hospital,boston,ma,united states,joslin diabetes center,boston,ma, United States, pediatric cancer biology program,papé family pediatric research institute,department of pediatrics,oregon health and science university,portland,or, United States, department of epidemiology and biostatistics,university of texas health science center,san antonio,tx, United States, department of radiation medicine,oregon health and science university,portland,or, United States, division of medical oncology,sidney kimmel comprehensive cancer center,johns hopkins university,baltimore,md, United States, division of pediatric oncology,sidney kimmel comprehensive cancer center,johns hopkins university,baltimore,md, United States, departments of anatomic pathology and molecular genetics,taussig cancer center and lerner research institute,cleveland clinic foundation,cleveland,oh, United States, the howard hughes medical institute and department of stem cell and regenerative biology,harvard university,cambridge,ma,united states,joslin diabetes center,boston,ma, United States, pediatric cancer biology program,papé family pediatric research institute,department of pediatrics,oregon health and science university,portland,or, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|