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.

journal_name

Cell

journal_title

Cell

authors

Scurr LL,Pupo GM,Becker TM,Lai K,Schrama D,Haferkamp S,Irvine M,Scolyer RA,Mann GJ,Becker JC,Kefford RF,Rizos H

doi

10.1016/j.cell.2010.04.021

subject

Has Abstract

pub_date

2010-05-14 00:00:00

pages

717-27

issue

4

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(10)00438-1

journal_volume

141

pub_type

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