Accession Number : AD1035584


Title :   Uncovering the Role of BMP Signaling in Melanocyte Development and Melanoma Tumorigenesis


Descriptive Note : Technical Report,01 Jul 2013,30 Jun 2016


Corporate Author : University of Massachusetts Medical School Worcester United States


Personal Author(s) : Ceol,Craig J


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1035584.pdf


Report Date : 01 Sep 2016


Pagination or Media Count : 101


Abstract : Melanoma is the most aggressive and lethal form of skin cancer. In 2013 over 75,000 Americans were diagnosed with melanoma, and nearly 10,000 died from this disease. It has been known for over a decade that mutations that over activate the BRAF and NRAS genes promote melanoma formation. At the same time it has also become clear that these mutations are not sufficient for melanoma formation and other genes are involved. Using genomic studies and cross-species comparisons, we identified the BMP factor GDF6 as a gene that may cooperate with mutant BRAF to promote melanoma. The aims of this grant are to determine if GDF6 does in fact cooperate with mutant BRAF and uncover the mechanisms by which GDF6 acts in melanomas and normal melanocytes. Toward these aims, we have used our zebra fish model to demonstrate cooperativity between GDF6 and mutant BRAF in accelerating melanoma onset. Furthermore, we have knocked down GDF6 in human melanoma cells, finding that loss of GDF6 causes cells to cease proliferating. These and other data suggest that GDF6 promotes melanoma progression and its withdrawal is detrimental to melanoma cell growth. We are currently investigating whether blocking GDF6 function is a viable therapeutic strategy.


Descriptors :   skin cancer , cell physiological processes , embryonic structures , stem cells , therapeutics , immune serums , gene expression , neoplasms , genomics , rodents , melanin , mutations , proteins


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE