The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters

Costessi, Adalberto; Mahrour, Nawel; Tijchon, Esther; Stunnenberg, Rieka; Stoel, Marieke A.; Jansen, Pascal W.T.C.; Sela, Dotan; Martin-Brown, Skylar; Washburn, Michael P.; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C.; Stunnenberg, Hendrik G.

doi:10.1038/emboj.2011.262

Cited by 61 publications

(82 citation statements)

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“…Targeting the Y/CCAAT box in cancer D Dolfini and R Mantovani transformed cells; the correlation is so impressive that in some tumors it is considered a prognostic marker (for a review see Eliseeva et al 71 and Costessi et al 133 ). Furthermore, the localization of YB-1 becomes strongly nuclear in tumor cells.…”

Section: The -Apparent -Paradox Of Y/ccaat Nf-y and Yb-1 In Cancermentioning

confidence: 99%

Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y?

Dolfini

Mantovani

2013

Cell Death Differ

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The Y box is an important sequence motif found in promoters and enhancers containing a CCAAT box -one of the few elements enriched in promoters of large sets of genes overexpressed in cancer. The search for the transcription factor(s) acting on it led to the biochemical purification of the nuclear factor Y (NF-Y) heterotrimer, and to the cloning -through the screening of expression libraries -of Y box-binding protein 1 (YB-1), an oncogene, overexpressed in aggressive tumors and associated with drug resistance. These two factors have been associated with Y/CCAAT-dependent activation of numerous growth-related genes, notably multidrug resistance protein 1. We review two decades of data indicating that NF-Y ultimately acts on Y/CCAAT in cancer cells, a notion recently confirmed by genome-wide data. Other features of YB-1, such as post-transcriptional control of mRNA biology, render it important in cancer biology.

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Section: The -Apparent -Paradox Of Y/ccaat Nf-y and Yb-1 In Cancermentioning

confidence: 99%

Targeting the Y/CCAAT box in cancer: YB-1 (YBX1) or NF-Y?

Dolfini

Mantovani

2013

Cell Death Differ

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“…Information about PRAME expression and its prognostic value in HL is very limited. In a study performed by Staege et al [16] it was demonstrated that PRAME has been found to be expressed only in cell lines belonging to patients with resistant HL [17] . In the study performed by Willenbrock et al [18] , when patients with HL were compared with those with anaplastic large cell lymphomas and B cell non-Hodgkin lymphoma, PRAME expression was found to be higher in HL.…”

Section: Prame Expression and Its Clinicalmentioning

confidence: 98%

PRAME Expression and Its Clinical Relevance in Hodgkin's Lymphoma

Erçolak¹,

Paydaş²,

Bağır³

et al. 2015

Acta Haematol

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Objectives: Although Hodgkin's lymphoma (HL) is one of the most curable cancers in adult patients, new targets have to be defined in cases resistant to traditional chemotherapy. The preferentially expressed antigen of melanoma (PRAME) is a cancer testis antigen and its expression is very scarce or absent in normal tissues. For this reason PRAME is a promising candidate for tumor immunotherapy. The aim of this study is to understand the correlation of PRAME expression with prognostic factors in HL, to determine the utility of PRAME as a targeted molecule for immunotherapy and to compare real-time polymerase chain reaction (real-time PCR) and immunohistochemistry (IHC) for the detection of PRAME. Methods: In 82 patients, PRAME was studied using real-time PCR and IHC. Data analyses were performed using statistical methods such as t test, Mann-Whitney U test, χ² test, Kaplan-Meier method, log-rank test and Cox regression analysis. Results: PRAME was detected in 15 (18.3%) patients using IHC and in 8 (9.8%) patients using real-time PCR. A correlation was found between PRAME positivity and higher International Prognostic Score (p = 0.039). PRAME positivity detected using real-time PCR was found to be correlated with shorter disease-free survival (DFS) and overall survival (OS, p = 0.0005). Discussion: The demonstration of PRAME especially in histiocytes and Reed-Sternberg cells may provide guidance for immunotherapy. Although PRAME positivity increases the risk for death (3.56), independent risk factors that affected DFS and OS occurred in advanced age and high-risk groups. Conclusion: Although real-time PCR is sensitive in the detection of PRAME, IHC can be another useful method. Despite the need for studies conducted on larger patient samples, PRAME expression is considered as a poor prognostic parameter in HL.

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“…Inhibition of cell cycle arrest and differentiation may explain why PRAMEpositive cells are selected for during cancer progression, and interference with RA signaling may be pivotal for the establishment and maintenance of cancer stem cell phenotypes [1,17]. Recent in vitro studies have identified PRAME as a subunit of E3 ubiquitin ligase, and DNAbinding analyses support a role for PRAME in NFY-mediated transcriptional regulation [18]. Regulation of PRAME expression is thought to be, at least in part, controlled by methylation and other epigenetic silencing mechanisms.…”

Section: Prame Biology and Potential Role In Cancermentioning

confidence: 99%