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Transcriptional regulation of ASK/Dbf4 in cutaneous melanoma is dependent on E2F1
Author(s) -
Nambiar Sandeep,
Mirmohammadsadegh Alireza,
Hassan Mohamed,
Hegemann Johannes H.,
Hengge Ulrich R.
Publication year - 2008
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2008.00730.x
Subject(s) - biology , ask price , melanoma , cancer research , transcriptional regulation , downregulation and upregulation , e2f1 , regulator , transcription factor , gene , genetics , economics , economy
Background: Melanoma is a complex genetic disease, the management of which will require an in‐depth understanding of the biology underlying its initiation and progression. Recently, we have reported the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggested upregulation of ASK/Dbf4 as a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma. As trans ‐acting factor binding is fundamental to understand the regulation of gene expression, this study focuses on characterization of the specific transcriptional regulation of ASK/Dbf4 in melanoma. Objective: We investigated whether ASK/Dbf4 is a transcriptional target of the important cell cycle regulator E2F1 in melanoma. Results: As evidenced by gel supershift assays on nuclear extracts from various melanoma cell lines (SK‐MEL‐28, MV3, M13, A375 and BLM), E2F1 bound to the ASK/Dbf4 minimal promoter (MP). In addition, cisplatin‐mediated abrogation of E2F1 binding to the ASK/Dbf4 MP resulted in a transcriptional decrease in ASK/Dbf4 . Further, the current study also demonstrated that ASK/Dbf4 regulation was refractory to UVB, a well‐known risk factor for melanoma. Conclusions: In summary, our study not only elucidated that ASK/Dbf4, a novel cell survival gene in melanoma was transcriptionally regulated by E2F1, but also that the induction of ASK/Dbf4 was refractory to UVB exposure suggesting that its upregulation was not an early event in melanomagenesis.