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

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 F. Kefford, Helen Rizos

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Citations (Scopus)

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-RAFV600E-induced senescence in human melanocytes.

Original languageEnglish
Pages (from-to)717-727
Number of pages11
JournalCell
Volume141
Issue number4
DOIs
Publication statusPublished - May 2010
Externally publishedYes

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