1: J Biol Chem. 2003 Jan 31;278(5):2983-9. Epub 2002 Nov 15. 

E2F proteins regulate MYCN expression in neuroblastomas.

Strieder V, Lutz W.

Institute of Molecular Biology and Tumor Research (IMT), Emil-Mannkopff-Strasse
2, 35033 Marburg, Germany.

Amplification of the MYCN gene, resulting in overexpression of MYCN,
distinguishes a subset of neuroblastomas with poor prognosis. The transcription
factors driving MYCN expression in neuroblastomas are unknown. In
transient-transfection assays, E2F-1, E2F-2, and E2F-3 activate a MYCN reporter
construct dependent on the presence of several putative E2F-binding sites. Using
chromatin immunoprecipitation, we show that E2F-1, E2F-2, and E2F-3 bind to the
proximal MYCN promoter in vivo, specifically in neuroblastoma cell lines
expressing MYCN. Inhibition of E2F activity in MYCN-amplified cells by the
overexpression of p16(INK4A) reduced MYCN expression. In addition, we provide
evidence that E2F proteins are involved in the negative regulation of MYCN by
TGF-beta and retinoic acid. These data suggest that E2F transcription factors
are critical for both the full activation and the repression of MYCN in
neuroblastomas.

PMID: 12438307 [PubMed - indexed for MEDLINE]


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2: J Pediatr Surg. 1998 Nov;33(11):1695-8. 

Fluorescence in situ hybridization analysis of chromosome 1p36 deletions in
human MYCN amplified neuroblastoma.

Komuro H, Valentine MB, Rowe ST, Kidd VJ, Makino S, Brodeur GM, Cohn SL, Look
AT.

Department of Experimental Oncology, St Jude Children's Research Hospital,
Memphis, Tennessee 38105-2794, USA.

BACKGROUND/PURPOSE: Deletion of the short arm of chromosome 1 (1p) is one of the
poor prognostic factors in human neuroblastomas. Recent studies have suggested
that one or more of the neuroblastoma tumor suppressor genes reside in this
region and have identified the shortest region of overlap (SRO) on 1p36. The
purpose of this study was to examine deletions of 1p in human neuroblastomas by
fluorescence in situ hybridization (FISH). METHODS: Two-color FISH analysis was
performed to detect chromosome 1p36 abnormalities in 42 MYCN-amplified
neuroblastomas. Four different probes from the 1p36 region, the E2F2, NPPA,
D1S160, and CDC2L1 loci were used for detection of 1p abnormalities. A repeat
sequence probe, which is specific for the heterochromatic region of chromosome 1
(pUC1.77), was used as a control. RESULTS: Large deletions of 1p36 were observed
in 31 (73.8%) of 42 tumors, whereas the remaining 11 (26.2%) showed no deletion.
In these 11 tumors, a translocation of 1p was found in one and a duplication of
1p was detected in another. CONCLUSIONS: A strong correlation between 1p
abnormalities and MYCN amplification was found in this study. MYCN-amplified
neuroblastomas were found to show large deletions of 1p encompassing the SRO.
FISH provided a rapid and reliable method to detect hemizygous deletions of 1p.

PMID: 9856898 [PubMed - indexed for MEDLINE]


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