@article{af598dd36a234124a52077ba68f6c827,
title = "Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability",
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 Mitfmi/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.",
author = "McGill, {Ga{\"e}l G.} and Martin Horstmann and Widlund, {Hans R.} and Jinyan Du and Gabriela Motyckova and Nishimura, {Emi K.} and Lin, {Yi Ling} and Sridhar Ramaswamy and William Avery and Ding, {Han Fei} and Jordan, {Siobh{\'a}n A.} and Jackson, {Ian J.} and Korsmeyer, {Stanley J.} and Golub, {Todd R.} and Fisher, {David E.}",
note = "Funding Information: We thank Wade Huber for adenovirus production and technical assistance; Cliff Takemoto with help in early aspects of this work; David Rowitch and members of the Rowitch lab for technical assistance with microscopy; Ruth Halaban for melanocytes and melanoma cells; and Scott Granter, Robert Martinez, Roydon Price, Junqing Cui, Min Wu, and other members of the Fisher lab for helpful contributions. We also thank Dr. Michael Greenberg, Dr. Christopher T. Walsh, and Dr. Junying Yuan for helpful comments. G.G.M. is supported by the Howard Hughes Medical Institute Predoctoral Fellowship and a Sandoz Fellowship. M.H. was supported by the Mildred-Scheel-Foundation of Deutsche Krebshilfe. H.R.W. is a Swedish Wenner-Gren postdoctoral fellow, S.R. is supported by a Harvard Medical School/National Institutes of Health Training Grant in Molecular Hematology, and S.A.J. was a European Molecular Biology Organization Fellow. This work was supported in part by grants from NIH (CA50239) to S.J.K.; Bristol-Myers Squibb, Millennium Pharmaceuticals, and Affymetrix, Inc. to T.R.G., and from NIH (AR43369 and AR45662) to D.E.F. D.E.F. is Jan and Charles Niremberg Fellow at the Dana-Farber Cancer Institute. This paper is dedicated to the memory of Mary Kaye Waldron (1972–1995).",
year = "2002",
month = jun,
day = "14",
doi = "10.1016/S0092-8674(02)00762-6",
language = "English (US)",
volume = "109",
pages = "707--718",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",
}