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发表于 2010-6-1 05:09 |显示全部帖子 |倒序浏览 |打印
A Temporarily Distinct Subpopulation
$ L. ~8 H8 B* y  C0 iof Slow-Cycling Melanoma Cells/ q0 E& z+ Q8 e8 f5 J9 R
Is Required for Continuous Tumor Growth
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, A2 A1 Y4 T# U; z7 VMelanomas are highly heterogeneous tumors, but the biological significance of their different subpopulations is not clear. Using the H3K4 demethylase JARID1B (KDM5B/PLU-1/RBP2-H1) as a biomarker, we have characterized a small subpopulation of slow-cycling melanoma cells that cycle with doubling times of >4 weeks within the rapidly proliferating main population. Isolated JARID1B-positive melanoma cells give rise to a highly proliferative progeny. Knockdown of JARID1B leads to an initial acceleration of tumor growth followed by exhaustion( X9 K9 V2 s/ R! w7 B+ q" R4 i% X
which suggests that the JARID1B-positive subpopulation is essential for continuous tumor growth. Expression of JARID1B is dynamically regulated and does not follow a hierarchical cancer stem cell model because JARID1B-negative cells can become positive and even single melanoma cells irrespective of selection are tumorigenic. These results suggest a new understanding of melanoma heterogeneity with tumor maintenance as a dynamic process mediated by a temporarily distinct subpopulation.
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