|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
These data demonstrate that PAX3 and PAX3-FKHR contain structurally distinct transcriptional activation domains and suggest that a consequent difference in function is important for oncogenesis.
|
7624119 |
1995 |
|
Carcinogenesis
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Alveolar tumors, for example, often possess a chromosomal translocation [t(2;13)(q35;q14)] that fuses the PAX3 gene in band 2q35 with the FKHR gene in band 13q14, creating a novel chimeric protein that could inappropriately activate normal targets of the PAX3 gene product, thereby contributing to tumorigenesis.
|
7636557 |
1995 |
|
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
To determine the role of the fusion protein in transcriptional regulation and oncogenesis, we identified the PAX3-FKHR fusion protein and characterized its function(s) as a transcription factor relative to wild-type PAX3.
|
7862145 |
1995 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
We have shown, however, that the structurally distinct transactivation domains of PAX3 and PAX3-FKHR differ 10- to 100-fold in their susceptibility to inhibition, thus elucidating a mechanism by which PAX3 gains enhanced function during oncogenesis.
|
8643596 |
1996 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
This cellular transformation in vitro will facilitate studies on the mechanism of PAX3-FKHR-induced oncogenesis.
|
8790412 |
1996 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
We hypothesize that PAX3-FKHR regulates downstream effector genes involved in rhabdomyosarcoma tumorigenesis.
|
9721857 |
1998 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
These results support the hypothesis that PAX3-FKHR interacts with IGF-II to play a critical role in the oncogenesis of rhabdomyosarcoma.
|
9766674 |
1998 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
We have demonstrated that synthetic repressors combining PAX3 DNA binding domains with different repression domains, KRAB or SNAG, are able to specifically inhibit malignant growth and suppress tumorigenesis in alveolar rhabdomyosarcoma tumor cells transformed by the translocation-derived chimeric transcriptional activator, PAX3-FKHR.
|
11164187 |
2001 |
|
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
Although PAX3-FKHR exhibits transforming activity in immortalized fibroblast cell lines, a direct role of this fusion protein in tumorigenesis in vivo has not been shown.
|
12242297 |
2002 |
|
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis.
|
12414908 |
2002 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Most strikingly, upregulated PAX7 expression is almost entirely restricted to cases without PAX3-FKHR or PAX7-FKHR fusion genes and may contribute to tumorigenesis in the absence of chimaeric PAX transcription factors.
|
12865925 |
2003 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
These findings of genes regulated by PAX3-FKHR will direct future biological and clinical investigation to important pathways contributing to ARMS tumorigenesis and progression.
|
15184910 |
2004 |
|
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
Expression of Pax3:Fkhr in muscle is necessary but not sufficient to initiate tumorigenesis at high frequency.
|
16140913 |
2005 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
These functional studies have advanced our understanding of the effects of PAX3 isoforms in melanocytes and their potential contribution in tumorigenesis.
|
16951170 |
2006 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
This review highlights recent advances in numerous areas of biomedical investigation that are providing new insights into the biology, molecular pathology, and translational science of ARMS: the identification of downstream targets of PAX3-FKHR and collaborating events in the process of tumorigenesis and metastasis; generation of animal models based on the gene fusion and collaborating events; development of new assays for diagnosis, prognosis, and detection of minimal disseminated disease; and exploration of immune recognition of this tumor and the fusion protein.
|
17311532 |
2007 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
In conclusion, we identified a selected set of biologically relevant genes modulated by PAX3-FKHR, and demonstrated that PAX3-FKHR contributes to the expression of MYCN and in turn MYCN collaborates with PAX3-FKHR in tumorigenesis.
|
18335505 |
2008 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
The results presented in this report not only suggest a possible mechanism by which the disregulation of Pax3-FOXO1 may contribute to tumorigenesis but also identify a novel target for the development of therapies for the treatment of ARMS.
|
19904978 |
2009 |
|
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
High expression of the PAX3-FKHR oncoprotein is required to promote tumorigenesis of human myoblasts.
|
19893043 |
2009 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
The aim of this study was to investigate the implication of Pax3 and Pax7 C-terminal isoforms during myogenic differentiation and tumorigenesis, since fusions involving these genes are commonly associated with alveolar rhabdomyosarcoma (ARMS).
|
21421465 |
2011 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Therefore we were unable to identify any contribution of up regulation of wild type FGFR4 to PAX3-FOXO1 driven tumorigenesis.
|
21882254 |
2012 |
|
Carcinogenesis
|
0.100 |
AlteredExpression
|
phenotype |
BEFREE |
When constantly expressed, PAX3-FOXO1 interfered with the muscle differentiation process, which presumably contributes to tumorigenesis.
|
24089019 |
2013 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Although associations between ARMS tumorigenesis and PAX3, PAX7, and FKHR are well recognized, the complete genetic etiology underlying RMS pathogenesis and progression remains unclear.
|
24551291 |
2014 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
These results indicate that the PAX3-NCOA2 fusion gene has a dual role in the tumorigenesis of RMS: promotion of the proliferation and inhibition of the myogenic differentiation of RMS cells.
|
24213582 |
2014 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression.
|
24334454 |
2014 |
|
Carcinogenesis
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
As PAX3-FOXO1 has proven chemically intractable, this study aims to identify targetable proteins that are downstream from or cooperate with PAX3-FOXO1 to support tumorigenesis.
|
26071485 |
2015 |