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.
journal_name
Celljournal_title
Cellauthors
Scurr LL,Pupo GM,Becker TM,Lai K,Schrama D,Haferkamp S,Irvine M,Scolyer RA,Mann GJ,Becker JC,Kefford RF,Rizos Hdoi
10.1016/j.cell.2010.04.021subject
Has Abstractpub_date
2010-05-14 00:00:00pages
717-27issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(10)00438-1journal_volume
141pub_type
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