Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia.

Cancer cell | Apr 13, 2010

The biologic and clinical significance of KIT overexpression that associates with KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that KIT mutations lead to MYC-dependent miR-29b repression and increased levels of the miR-29b target Sp1 in KIT-driven leukemia. Sp1 enhances its own expression by participating in a NFkappaB/HDAC complex that further represses miR-29b transcription. Upregulated Sp1 then binds NFkappaB and transactivates KIT. Therefore, activated KIT ultimately induces its own transcription. Our results provide evidence that the mechanisms of Sp1/NFkappaB/HDAC/miR-29b-dependent KIT overexpression contribute to leukemia growth and can be successfully targeted by pharmacological disruption of the Sp1/NFkappaB/HDAC complex or synthetic miR-29b treatment in KIT-driven AML.

Pubmed ID: 20385359 RIS Download

Mesh terms: Cell Line, Tumor | Chromosomes, Human, Pair 7 | Gene Expression Regulation, Neoplastic | Genetic Vectors | Histone Deacetylases | Homeostasis | Humans | Immunoglobulins | Leukemia, Myeloid | MicroRNAs | NF-kappa B | Proto-Oncogene Proteins c-kit | Transcription, Genetic

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: P50 CA140158
  • Agency: NCI NIH HHS, Id: R01 CA102031
  • Agency: NCI NIH HHS, Id: CA140158
  • Agency: NCI NIH HHS, Id: CA102031
  • Agency: NCI NIH HHS, Id: CA101140
  • Agency: NCI NIH HHS, Id: U10 CA077658
  • Agency: NCI NIH HHS, Id: CA077658
  • Agency: NCI NIH HHS, Id: U24 CA114725
  • Agency: NCI NIH HHS, Id: R01 CA095512
  • Agency: NCI NIH HHS, Id: U10 CA101140
  • Agency: NCI NIH HHS, Id: R01 CA102031-07
  • Agency: NCRR NIH HHS, Id: UL1 RR025755
  • Agency: NCI NIH HHS, Id: CA114725

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.