title: IGFBP7 is not required for B-RAF-induced melanocyte senescence.
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.
authors.affiliation: 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
authors.forename: Lyndee L
authors.initials: LL
authors.lastname: Scurr
authors.forename: Gulietta M
authors.initials: GM
authors.lastname: Pupo
authors.forename: Therese M
authors.initials: TM
authors.lastname: Becker
authors.forename: Ken
authors.initials: K
authors.lastname: Lai
authors.forename: David
authors.initials: D
authors.lastname: Schrama
authors.forename: Sebastian
authors.initials: S
authors.lastname: Haferkamp
authors.forename: Mal
authors.initials: M
authors.lastname: Irvine
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Mann
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.forename: Helen
authors.initials: H
authors.lastname: Rizos
mesh_terms: 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*
chemical_list: D048493:Proto-Oncogene Proteins B-raf