PMID- 16778208
OWN - NLM
STAT- MEDLINE
DCOM- 20060810
LR  - 20220318
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 12
DP  - 2006 Jun 15
TI  - Notch3 gene amplification in ovarian cancer.
PG  - 6312-8
AB  - Gene amplification is one of the common mechanisms that activate oncogenes. In 
      this study, we used single nucleotide polymorphism array to analyze genome-wide 
      DNA copy number alterations in 31 high-grade ovarian serous carcinomas, the most 
      lethal gynecologic neoplastic disease in women. We identified an amplicon at 
      19p13.12 in 6 of 31 (19.5%) ovarian high-grade serous carcinomas. This 
      amplification was validated by digital karyotyping, quantitative real-time PCR, 
      and dual-color fluorescence in situ hybridization (FISH) analysis. Comprehensive 
      mRNA expression analysis of all 34 genes within the minimal amplicon identified 
      Notch3 as the gene that showed most significant overexpression in amplified 
      tumors compared with nonamplified tumors. Furthermore, Notch3 DNA copy number is 
      positively correlated with Notch3 protein expression based on parallel 
      immunohistochemistry and FISH studies in 111 high-grade tumors. Inactivation of 
      Notch3 by both gamma-secretase inhibitor and Notch3-specific small interfering 
      RNA suppressed cell proliferation and induced apoptosis in the cell lines that 
      overexpressed Notch3 but not in those with minimal amount of Notch3 expression. 
      These results indicate that Notch3 is required for proliferation and survival of 
      Notch3-amplified tumors and inactivation of Notch3 can be a potential therapeutic 
      approach for ovarian carcinomas.
FAU - Park, Joon T
AU  - Park JT
AD  - Department of Gynecology, The Johns Hopkins Medical Institutions, Baltimore, 
      Maryland 21231, USA.
FAU - Li, Mei
AU  - Li M
FAU - Nakayama, Kentaro
AU  - Nakayama K
FAU - Mao, Tsui-Lien
AU  - Mao TL
FAU - Davidson, Ben
AU  - Davidson B
FAU - Zhang, Zhen
AU  - Zhang Z
FAU - Kurman, Robert J
AU  - Kurman RJ
FAU - Eberhart, Charles G
AU  - Eberhart CG
FAU - Shih, Ie-Ming
AU  - Shih IeM
FAU - Wang, Tian-Li
AU  - Wang TL
LA  - eng
GR  - R01 CA103937/CA/NCI NIH HHS/United States
GR  - R01 CA103937-03/CA/NCI NIH HHS/United States
GR  - CA103937/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (NOTCH3 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptor, Notch3)
RN  - 0 (Receptors, Notch)
SB  - IM
MH  - Chromosomes, Human, Pair 19/genetics
MH  - Female
MH  - Gene Amplification
MH  - Gene Dosage
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Ovarian Neoplasms/*genetics/metabolism
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single Nucleotide
MH  - RNA, Messenger/biosynthesis/genetics
MH  - RNA, Small Interfering/genetics
MH  - Receptor, Notch3
MH  - Receptors, Notch/*genetics
EDAT- 2006/06/17 09:00
MHDA- 2006/08/11 09:00
CRDT- 2006/06/17 09:00
PHST- 2006/06/17 09:00 [pubmed]
PHST- 2006/08/11 09:00 [medline]
PHST- 2006/06/17 09:00 [entrez]
AID - 66/12/6312 [pii]
AID - 10.1158/0008-5472.CAN-05-3610 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Jun 15;66(12):6312-8. doi: 10.1158/0008-5472.CAN-05-3610.