[HTML][HTML] IGFBP7 is not required for B-RAF-induced melanocyte senescence
Cell, 2010•cell.com
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 …
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 …
Summary
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-RAFV600E-induced senescence in human melanocytes.
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