Journal Article

Identification and functional characterization of <i>ASK/Dbf4</i>, a novel cell survival gene in cutaneous melanoma with prognostic relevance

Sandeep Nambiar, Alireza Mirmohammadsadegh, Mohamed Hassan, Rodrigo Mota, Alessandra Marini, Amine Alaoui, Andrea Tannapfel, Johannes H. Hegemann and Ulrich R. Hengge

in Carcinogenesis

Volume 28, issue 12, pages 2501-2510
Published in print December 2007 | ISSN: 0143-3334
Published online September 2007 | e-ISSN: 1460-2180 | DOI:
Identification and functional characterization of ASK/Dbf4, a novel cell survival gene in cutaneous melanoma with prognostic relevance

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  • Clinical Cytogenetics and Molecular Genetics


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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.

Journal Article.  4689 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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