IGFBP7 is not required for B-RAF-induced melanocyte senescence.
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.
Scurr
Lyndee L
LL
Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales 2145, Australia. lyndee_scurr@wmi.usyd.edu.au
Pupo
Gulietta M
GM
Becker
Therese M
TM
Lai
Ken
K
Schrama
David
D
Haferkamp
Sebastian
S
Irvine
Mal
M
Scolyer
Richard A
RA
Mann
Graham J
GJ
Becker
Jürgen C
JC
Kefford
Richard F
RF
Rizos
Helen
H
D045744:Cell Line, Tumor; D016922:Cellular Senescence; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf; D012878:Skin Neoplasms / Q000378:metabolism*
D048493:Proto-Oncogene Proteins B-raf