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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2007-12-6
pubmed:abstractText
Malignant melanoma is one of the most aggressive and invasive metastatic tumors derived from melanocytes that have undergone malignant transformation by acquisition of genetic and epigenetic alterations. Oligonucleotide microarray-based screening of distinct stages in the tumor progression model of cutaneous melanoma identified ASK/Dbf4, as a novel determinant for melanoma development. Quantitative real-time polymerase chain reaction-based confirmation of ASK/Dbf4 on a series of benign nevi, dysplastic nevi, primary cutaneous melanomas and cutaneous melanoma metastases; and a number of other controls using normal human melanocytes as calibrator not only revealed a melanoma-specific over-expression but also revealed that higher ASK/Dbf4-expressing melanomas were associated with lower relapse-free survival. Additionally, we also confirmed the observed over-expression of ASK/Dbf4 in melanoma using western blot analysis and immunohistochemistry. As ASK/Dbf4 is known to be a cyclin-like regulatory subunit of mammalian Cdc7 from the studies in yeast, the present study investigated its role in melanoma cells. In keeping with its expected role, our data suggest that up-regulated ASK/Dbf4 is localized in the nucleus and binds to human Cdc7 to form Cdc7-ASK/Dbf4 complexes in several analyzed melanoma cell lines. Further, we demonstrate that small interfering RNA-mediated depletion of ASK/Dbf4 retarded melanoma cell survival and proliferation. In summary, we report the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggest that up-regulation of ASK/Dbf4 is a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2501-10
pubmed:dateRevised
2010-5-26
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Identification and functional characterization of ASK/Dbf4, a novel cell survival gene in cutaneous melanoma with prognostic relevance.
pubmed:affiliation
Department of Dermatology, Heinrich-Heine-University, Moorenstrasse 5, Duesseldorf D-40225, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't