IHOP genetics pubmed

FOXD3 is a mutant B-RAF-regulated inhibitor of G(1)-S progression in melanoma cells.
Abel EV, Aplin AE
Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
The forkhead box transcription factor FOXD3 is a stemness factor that prevents the production of melanocyte progenitors from the developing neural crest; however, its role in human cancers is not known. Transformation of melanocytes gives rise to melanoma. In two thirds of melanomas, the serine [?]/threonine kinase B-RAF is mutated to a constitutively active form. Here, we show that FOXD3 levels are upregulated following attenuation of B-RAF and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) signaling in mutant B-RAF harboring human melanoma cells. This effect was selective because FOXD3 was not upregulated following MEK inhibition in wild-type B-RAF melanoma cells and mutant B-RAF thyroid carcinoma cells. Ectopic FOXD3 expression potently inhibited melanoma cell growth without altering mutant B-RAF activation of ERK1/2. Inhibition of cell growth was due to a potent G(1) cell cycle arrest and was associated with p53-dependent upregulation of p21(Cip1). FOXD3-induced cell cycle arrest was prevented by p53 depletion and, to a lesser extent, p21(Cip1) depletion. These studies show that FOXD3 is suppressed by B-RAF, uncover a novel role and mechanism for FOXD3 as a negative cell cycle regulator, and have implications for the repression of melanocytic lineage cells.

Cancer Res. (2010)

PMID: 20332228

About garyskeete

ASHWORTH MEDICINE-Professional Medical Assisting, Doctor of Science,Legal Assistant Diploma BSc Criminal Justice PhD Computational Neuroscience MD DSC Epigenetics
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