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The Role of SWI/SNF Chromatin Remodeling Complex in Melanoma

Keenen, Bridget
http://rave.ohiolink.edu/etdc/view?acc_num=mco1271819328

Abstract Details

2010, Doctor of Philosophy in Biomedical Sciences (Ph.D.), University of Toledo, College of Medicine.
The microphthalmia-associated transcription factor (MITF) promotes melanocyte differentiation and cell cycle arrest. Paradoxically, MITF also promotes melanoma survival and proliferation, acting like a lineage survival oncogene. Thus, it is critically important to understand the mechanisms that regulate MITF activity in melanoma cells. SWI/SNF chromatin remodeling enzymes are multiprotein complexes composed of one of two related ATPases, BRG1 or BRM, and 9-12 associated factors (BAFs). We previously determined that BRG1 interacts with MITF to promote melanocyte differentiation. However, it was unclear whether SWI/SNF enzymes regulate the expression of different classes of MITF target genes in melanoma. In this study, we characterized SWI/SNF subunit expression in melanoma cells and observed down-regulation of BRG1 or BRM, but not concomitant loss of both ATPases. Re-introduction of BRG1 in BRG1 deficient SK-MEL5 cells enhanced expression of differentiation specific MITF target genes and resistance to cisplatin. Down-regulation of the single ATPase, BRM, in SK-MEL5 cells inhibited expression of both differentiation specific and pro-proliferative MITF target genes and inhibited tumorigenicity in vitro. Our data suggest that heterogeneous SWI/SNF complexes composed of either the BRG1 or BRM subunit promote expression of distinct and overlapping MITF target genes and that at least one ATPase is required for melanoma tumorigenicity.
Ivana de la Serna, PhD (Committee Chair)
Randall Ruch, PhD (Committee Member)
Randall Worth, PhD (Committee Member)
Jean Overmeyer, PhD (Committee Member)
Khew-Voon Chin, PhD (Committee Member)
176 p.
Molecular Biology
SWI/SNF; BRG1; Melanoma; BRM

Recommended Citations

Citations

  • Keenen, B. (2010). The Role of SWI/SNF Chromatin Remodeling Complex in Melanoma [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1271819328

    APA Style (7th edition)

  • Keenen, Bridget. The Role of SWI/SNF Chromatin Remodeling Complex in Melanoma. 2010. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1271819328.

    MLA Style (8th edition)

  • Keenen, Bridget. "The Role of SWI/SNF Chromatin Remodeling Complex in Melanoma." Doctoral dissertation, University of Toledo, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1271819328

    Chicago Manual of Style (17th edition)

mco1271819328
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© 2010, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.