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Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE45480 | GEO | 2013/03/26

SECONDARY ACCESSION(S): PRJNA194133

REPOSITORIES: GEO

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Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma.

Project description:Neuroblastoma is an embryonal malignancy of the sympathetic nervous system. Spontaneous regression and differentiation of neuroblastoma is observed in a subset of patients, and has been suggested to represent delayed activation of physiologic molecular programs of fetal neuroblasts. Homeobox genes constitute an important family of transcription factors, which play a fundamental role in morphogenesis and cell differentiation during embryogenesis. In this study, we demonstrate that expression of the majority of the human HOX class I homeobox genes is significantly associated with clinical covariates in neuroblastoma using microarray expression data of 649 primary tumors. Moreover, a HOX gene expression-based classifier predicted neuroblastoma patient outcome independently of age, stage and MYCN amplification status. Among all HOX genes, HOXC9 expression was most prominently associated with favorable prognostic markers. Most notably, elevated HOXC9 expression was significantly associated with spontaneous regression in infant neuroblastoma. Re-expression of HOXC9 in three neuroblastoma cell lines led to a significant reduction in cell viability, and abrogated tumor growth almost completely in neuroblastoma xenografts. Neuroblastoma growth arrest was related to the induction of programmed cell death, as indicated by an increase in the sub-G1 fraction and translocation of phosphatidylserine to the outer membrane. Programmed cell death was associated with the release of cytochrome c from the mitochondria into the cytosol and activation of the intrinsic cascade of caspases, indicating that HOXC9 re-expression triggers the intrinsic apoptotic pathway. Collectively, our results show a strong prognostic impact of HOX gene expression in neuroblastoma, and may point towards a role of Hox-C9 in neuroblastoma spontaneous regression.

| S-EPMC3668636 | biostudies-literature

Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-03-26 | E-GEOD-45480 | biostudies-arrayexpress

Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma [tumor_genex_44k]

Project description:Single-color gene expression profiles from 649 neuroblastoma tumors were generated using 44K oligonucleotide microarrays. We aimed at determining the association of class I HOX gene expression patterns with prognostic markers in neuroblastoma.We investigated the functional consequences of HOXC9 re-expression on neuroblastoma growth and programmed cell death. One-color gene expression analysis. Single-color gene expression profiles from 649 neuroblastoma tumors were generated using 44K oligonucleotide microarrays. Stages were classified according to the International Neuroblastoma Staging System. The expression patterns of the 39 class I HOX genes were analyzed in 649 neuroblastoma samples by microarrays, and the association with prognostic markers was determined.

2013-03-28 | E-GEOD-45547 | biostudies-arrayexpress

Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma [aCGH_1M]

Project description:Oligonucleotide aCGH profiles from 209 neuroblastoma tumor samples were generated using 44K, 105K or 1M microarrays. The 209th sample is represented by Sample GSM634116. Two-color array-based comparative genome hybridization (aCGH)

2013-03-26 | E-GEOD-45477 | biostudies-arrayexpress

Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma [aCGH_105k]

2013-03-26 | E-GEOD-45478 | biostudies-arrayexpress

Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma [aCGH_44k]

2013-03-26 | E-GEOD-45476 | biostudies-arrayexpress

Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma [tumor_genex_44k]

2013-03-28 | GSE45547 | GEO

Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma [aCGH_44k]

Project description:Oligonucleotide aCGH profiles from 209 neuroblastoma tumor samples were generated using 44K, 105K or 1M microarrays. The 209th sample is represented by Sample GSM634116.

2013-03-26 | GSE45476 | GEO

Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma [aCGH_105k]

Project description:Oligonucleotide aCGH profiles from 209 neuroblastoma tumor samples were generated using 44K, 105K or 1M microarrays. The 209th sample is represented by Sample GSM634116.

2013-03-26 | GSE45478 | GEO

Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma [aCGH_1M]

Project description:Oligonucleotide aCGH profiles from 209 neuroblastoma tumor samples were generated using 44K, 105K or 1M microarrays. The 209th sample is represented by Sample GSM634116.

2013-03-26 | GSE45477 | GEO

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