These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Growth factors rescue cutaneous melanoma cells from apoptosis induced by knockdown of mutated (V 600 E) B-RAF.
    Author: Christensen C, Guldberg P.
    Journal: Oncogene; 2005 Sep 15; 24(41):6292-302. PubMed ID: 16007203.
    Abstract:
    Constitutive activation of the RAS-RAF-MEK-ERK signaling cascade is a hallmark of cutaneous malignant melanoma. A single activating mutation (c.1799 T>A; p.V 600 E) in the gene encoding the serine/threonine kinase B-RAF occurs in >60% of the tumors. Previous work has shown that knockdown of (V 600 E)B-RAF by RNA interference induces a variety of phenotypic changes in cultured melanoma cells, including lower proliferation rates, reduced anchorage-independent growth and apoptosis. Here, we show that the majority of melanomas harboring the (V 600 E)B-RAF mutation have retained the wild-type (WT) B-RAF allele, and that these cells can be rescued from the effects of (V 600 E)B-RAF knockdown by stimulation with growth factors. Ectopic expression of short hairpin RNAs specifically suppressing (V 600 E)B-RAF in melanoma cell lines reduced colony formation by approximately 80%. This response could be rescued by basic fibroblast growth factor, hepatocyte growth factor or, to a lesser extent, endothelin-1. Rescue with growth factors was not possible in cell lines lacking (WT)B-RAF. Single-cell clones with efficient knockdown of (V 600 E)B-RAF could be propagated in the presence of basic fibroblast growth factor but underwent apoptosis or senescence-like growth arrest upon withdrawal of this growth factor. The ability of growth factors to modulate the response of (V 600 E)B-RAF knockdown in melanoma cells may have both experimental and therapeutic implications.
    [Abstract] [Full Text] [Related] [New Search]