Portal de Periódicos da CAPES

IGFBP7 Is Not Required for B-RAF-Induced Melanocyte Senescence

2010; Cell Press; Volume: 141; Issue: 4 Linguagem: Inglês

10.1016/j.cell.2010.04.021

1097-4172

Lyndee L. Scurr, Gulietta M. Pupo, Therese M. Becker, Ken Lai, David Schrama, Sebastian Haferkamp, Mal Irvine, Richard A. Scolyer, Graham J. Mann, Jürgen C. Becker, Richard Kefford, Helen Rizos,

Cancer-related Molecular Pathways

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.