Abstract：
:Kit/SCF signaling and Mitf-dependent transcription are both essential for melanocyte development and pigmentation. To identify Mitf-dependent Kit transcriptional targets in primary melanocytes, microarray studies were undertaken. Among identified targets was BCL2, whose germline deletion produces melanocyte loss and which exhibited phenotypic synergy with Mitf in mice. BCL2's regulation by Mitf was verified in melanocytes and melanoma cells and by chromatin immunoprecipitation of the BCL2 promoter. Mitf also regulates BCL2 in osteoclasts, and both Mitf(mi/mi) and Bcl2(-/-) mice exhibit severe osteopetrosis. Disruption of Mitf in melanocytes or melanoma triggered profound apoptosis susceptible to rescue by BCL2 overexpression. Clinically, primary human melanoma expression microarrays revealed tight nearest neighbor linkage for MITF and BCL2. This linkage helps explain the vital roles of both Mitf and Bcl2 in the melanocyte lineage and the well-known treatment resistance of melanoma.
journal_name
Celljournal_title
Cellauthors
McGill GG,Horstmann M,Widlund HR,Du J,Motyckova G,Nishimura EK,Lin YL,Ramaswamy S,Avery W,Ding HF,Jordan SA,Jackson IJ,Korsmeyer SJ,Golub TR,Fisher DEdoi
10.1016/s0092-8674(02)00762-6subject
Has Abstractpub_date
2002-06-14 00:00:00pages
707-18issue
6eissn
0092-8674issn
1097-4172pii
S0092867402007626journal_volume
109pub_type
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