TY - JOUR
T1 - IGFBP7 is not required for B-RAF-induced melanocyte senescence
AU - Scurr, Lyndee L.
AU - Pupo, Gulietta M.
AU - Becker, Therese M.
AU - Lai, Ken
AU - Schrama, David
AU - Haferkamp, Sebastian
AU - Irvine, Mal
AU - Scolyer, Richard A.
AU - Mann, Graham J.
AU - Becker, Jürgen C.
AU - Kefford, Richard F.
AU - Rizos, Helen
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77952479288&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2010.04.021
DO - 10.1016/j.cell.2010.04.021
M3 - Article
C2 - 20478260
AN - SCOPUS:77952479288
SN - 0092-8674
VL - 141
SP - 717
EP - 727
JO - Cell
JF - Cell
IS - 4
ER -