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Scurr, LL; Pupo, GM; Becker, TM; Lai, K; Schrama, D; Haferkamp, S; Irvine, M; Scolyer, RA; Mann, GJ; Becker, JC; Kefford, RF; Rizos, H.
IGFBP7 is not required for B-RAF-induced melanocyte senescence.
Cell. 2010; 141(4):717-727
Doi: 10.1016/j.cell.2010.04.021
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- Co-Autor*innen der Med Uni Graz
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Becker Jürgen Christian
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Schrama David
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- Abstract:
- Induction of senescence permanently restricts cellular proliferation after oncogenic stimulation thereby acting as a potent barrier to tumor development. The relevant effector proteins may therefore be fundamental to cancer development. A recent study identified IGFBP7 as a secreted factor mediating melanocyte senescence induced by oncogenic B-RAF, which is found commonly in cutaneous nevi. In contrast to the previous report, we demonstrate that B-RAF signaling does not induce IGFBP7 expression, nor the expression of the IGFBP7 targets, BNIP3L, SMARCB1, or PEA15, in human melanocytes or fibroblasts. We also found no correlation between B-RAF mutational status and IGFBP7 protein expression levels in 22 melanoma cell lines, 90 melanomas, and 46 benign nevi. Furthermore, using a lentiviral silencing strategy we show that B-RAF induces senescence in melanocytes and fibroblasts, irrespective of the presence of IGFBP7. Therefore, we conclude that the secreted protein IGFBP7 is dispensable for B-RAF(V600E)-induced senescence in human melanocytes.
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Cell Aging -
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Cell Line, Tumor -
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Humans -
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Melanocytes - cytology Melanocytes - metabolism
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Melanoma - metabolism
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Proto-Oncogene Proteins B-raf -
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Skin Neoplasms - metabolism