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Identification of a novel 12p13.3 amplicon in nasopharyngeal carcinoma
The Journal of pathology, 2010, Vol.220 (1), p.97-107
Or, Yvonne Y.Y
Chung, Grace T.Y
To, Ka-Fai
Chow, Chit
Choy, Kwong-Wai
Tong, Carol Y.K
Leung, Alice W.C
Hui, Angela B.Y
Tsao, Sai-Wah
Ng, Ho-Keung
Yip, Timothy T.C
Busson, Pierre
Lo, Kwok-Wai
2010
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Or, Yvonne Y.Y
Chung, Grace T.Y
To, Ka-Fai
Chow, Chit
Choy, Kwong-Wai
Tong, Carol Y.K
Leung, Alice W.C
Hui, Angela B.Y
Tsao, Sai-Wah
Ng, Ho-Keung
Yip, Timothy T.C
Busson, Pierre
Lo, Kwok-Wai
Titel
Identification of a novel 12p13.3 amplicon in nasopharyngeal carcinoma
Ist Teil von
The Journal of pathology, 2010, Vol.220 (1), p.97-107
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2010
Quelle
MEDLINE
Beschreibungen/Notizen
Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer commonly occurring in southern China. To decipher the molecular basis of this cancer, we performed high-resolution array CGH analysis on eight tumour lines and 10 primary tumours to identify the genes involved in NPC tumorigenesis. In this study, multiple regions of gain were consistently found at 1q21-q24, 7q11-12, 7q21-22., 11q13, 12p13, 12q13, 19p13 and 19q13. Importantly, a 2.1 Mb region at 12p13.31 was highly amplified in a NPC xenograft, xeno-2117. By FISH mapping, we have further delineated the amplicon to a 1.24 region flanked by RP11-319E16 and RP11-433J6. Copy number gains of this amplicon were confirmed in 21/41 (51%) primary tumours, while three cases (7.3%) showed high copy number amplification. Among the 13 genes within this amplicon, three candidate genes, lymphotoxin beta receptor (LTβR), tumour necrosis factor receptor superfamily memeber 1A (TNFRSF1R) and FLJ10665, were specifically over-expressed in the NPC xenograft with 12p13.3 amplification. However, only LTβR was frequently over-expressed in primary tumours. LTβR is a member of the TNF family of receptors, which can modulate NF-κB signalling pathways. Over-expression of LTβR in nasopharyngeal epithelial cells resulted in an increase of NF-κB activity and cell proliferation. In vivo study showed that suppression of LTβR by siRNA led to growth inhibition in the NPC tumour with 12p13.3 amplification. These findings implied that LTβR is a potential NPC-associated oncogene within the 12p13.3 amplicon and that its alteration is important in NPC tumorigenesis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sprache
Englisch
Identifikatoren
ISSN: 0022-3417
eISSN: 1096-9896
DOI: 10.1002/path.2609
Titel-ID: cdi_proquest_miscellaneous_734176105
Format
–
Schlagworte
12p13.3 amplicon
,
Animals
,
array CGH
,
Chromosomes, Human, Pair 12 - genetics
,
Comparative Genomic Hybridization
,
Epstein-Barr virus
,
Gene Amplification
,
Gene Expression Regulation, Neoplastic
,
Gene Knockdown Techniques
,
Humans
,
In Situ Hybridization, Fluorescence
,
LTβR
,
Lymphotoxin beta Receptor - biosynthesis
,
Lymphotoxin beta Receptor - genetics
,
Mice
,
Mice, Nude
,
nasopharyngeal carcinoma
,
Nasopharyngeal Neoplasms - genetics
,
Nasopharyngeal Neoplasms - metabolism
,
Nasopharyngeal Neoplasms - pathology
,
Neoplasm Proteins - biosynthesis
,
Neoplasm Proteins - genetics
,
Neoplasm Transplantation
,
NF-kappa B - metabolism
,
oncogene
,
Oncogenes
,
Reverse Transcriptase Polymerase Chain Reaction - methods
,
Signal Transduction - genetics
,
Signal Transduction - physiology
,
Transcription, Genetic
,
Transplantation, Heterologous
,
Tumor Cells, Cultured
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