JunB expression is a common feature of CD30+ lymphomas and lymphomatoid papulosis

Rassidakis, George Z.; Thomaides, Athanasios; Atwell, Coralyn; Ford, R.; Jones, Dan; Claret, François X.; Medeiros, L. Jeffrey

doi:10.1038/modpathol.3800419

Cited by 70 publications

(61 citation statements)

References 17 publications

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“…On the other hand, we presently demonstrate that silencing JunB in c-Jun knockout cells resulted in a p53-independent cell cycle arrest and apoptosis induction, indicating that c-Jun is critical for the JunB antiproliferative effect and tumor suppressor action, and that in cells lacking c-Jun, JunB can act as a tumor promoter. In support of this hypothesis, genetic experiments have demonstrated that JunB can replace c-Jun during mouse development (Passegue et al, 2002), and analysis of human samples showed that JunB is overexpressed in certain types of cancer (Mao et al, 2003;Rassidakis et al, 2005). Therefore, we speculate that if c-Jun can be maintained inactive, JunB could be a good target for cancer intervention.…”

Section: Discussionmentioning

confidence: 70%

“…On the other hand, the role of JunB in tumor development is less defined. Overexpression of JunB has been reported in human cancers (Mao et al, 2003;Rassidakis et al, 2005), whereas several studies indicated that JunB can inhibit cellular transformation acting as a tumor suppressor in humans and mice (Joseloff and Bowden, 1997;Szremska et al, 2003;Passegue et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Targeting c-Jun and JunB proteins as potential anticancer cell therapy

et al. 2007

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The activating protein-1 transcription factor, in particular the Jun proteins play critical roles in the regulation of cell proliferation and tumor progression. To study the potential clinical relevance of interfering with JunB expression, we generated retroviruses expressing short hairpin RNA. Reduction of JunB levels causes increased proliferation and tumorigenicity in wild-type murine fibroblasts, whereas in c-Jun knockout cells p53-independent cell cycle arrest and apoptosis are induced. Using melanoma-derived B16-F10 cancer cells the combination of JunB knockdown and c-Jun/JNK inactivation leads to cell cycle arrest and apoptosis-inducing factor-dependent apoptosis. Furthermore, the combined treatment extends survival of mice inoculated with the tumor cells. These results indicate that in the absence of c-Jun, JunB can act as a tumor promoter and inactivation of both, c-Jun and JunB, could provide a valuable strategy for antitumor intervention.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Targeting c-Jun and JunB proteins as potential anticancer cell therapy

et al. 2007

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“…JunB is expressed at high levels in Hodgkin's lymphoma and T-cell malignancies (Mao et al, 2003;Rassidakis et al, 2005). In contrast, it is not detectable in most human B-lymphoid malignancies and silenced in advanced stages of myeloid leukemia (Yang et al, 2003;Szremska et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, JunB is altered in human lymphoid malignancies. JunB is overexpressed in Hodgkin's lymphoma and in T-cell tumors, but only expressed at low levels or entirely missing in B-lymphoid malignancies (Mao et al, 2003;Szremska et al, 2003;Rassidakis et al, 2005). This observation is remarkable, as AP-1 family members are generally expressed at high levels in transformed cells (Wu et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

JunB is a gatekeeper for B-lymphoid leukemia

et al. 2007

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Loss of JunB has been observed in human leukemia and lymphoma, but it remains unknown, whether this loss is relevant to disease progression. Here, we investigated the consequences of JunB deficiency using Abelson-induced B-lymphoid leukemia as a model system. Mice deficient in JunB expression succumbed to Abelson-induced leukemia with increased incidence and significantly reduced latency. Similarly, bcr/abl p185-transformed JunB-deficient (junB D/D ) cells induced leukemia in RAG2 À/À mice displaying a more malignant phenotype. These observations indicated that cell intrinsic effects within the junB D/D tumor cells accounted for the accelerated leukemia development. Indeed, explantated bcr/abl p185 transformed junB D/D cells proliferated faster than the control cells. The proliferative advantage emerged slowly after the initial transformation process and was associated with increased expression levels of the cell cycle kinase cdk6 and with decreased levels of the cell cycle inhibitor p16 INK4a . These alterations were due to irreversible reprogramming of the cell, because -once established -accelerated disease induced by junB D/D cells was not reverted by re-introducing JunB. Consistent with this observation, we found that the p16 promoter was methylated. Thus, JunB functions as a gatekeeper during tumor evolution. In its absence, transformed leukemic cells acquire an enhanced proliferative capacity, which presages a more malignant disease.

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“…Deregulated CD30 expression in ALCL has been linked to activation of transcription factors of the AP-1 family, including c-Jun and JunB. 17,18 Regarding the expression of transcription factors involved in the regulation of the TCR/CD3 complex in CD30 + lymphoproliferations, Geissinger et al identified some defects (involving especially TCF-1 and TCF1a/LEF-1) in the whole group of CD30 + cases; however, in the absence of clear-cut correlations at the level of single cases they concluded that transcriptional dysfunction is probably not the primary cause of TCR/CD3 loss.…”

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confidence: 99%