Notch3 gene amplification in ovarian cancer

Joon T. Park, Mei Li, Kentaro Nakayama, Tsui Lien Mao, Ben Davidson, Zhen Zhang, Robert J Kurman, Charles G Eberhart, Ie Ming Shih, Tian-Li Wang

Research output: Contribution to journalArticle

Abstract

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 γ-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.

Original languageEnglish (US)
Pages (from-to)6312-6318
Number of pages7
JournalCancer Research
Volume66
Issue number12
DOIs
StatePublished - Jun 15 2006

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Gene Amplification
Ovarian Neoplasms
Carcinoma
Fluorescence In Situ Hybridization
Neoplasms
Female Genital Diseases
Karyotyping
Amyloid Precursor Protein Secretases
DNA
Oncogenes
Small Interfering RNA
Genes
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
Color
Immunohistochemistry
Cell Proliferation
Genome
Apoptosis
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Park, J. T., Li, M., Nakayama, K., Mao, T. L., Davidson, B., Zhang, Z., ... Wang, T-L. (2006). Notch3 gene amplification in ovarian cancer. Cancer Research, 66(12), 6312-6318. https://doi.org/10.1158/0008-5472.CAN-05-3610

Notch3 gene amplification in ovarian cancer. / Park, Joon T.; Li, Mei; Nakayama, Kentaro; Mao, Tsui Lien; Davidson, Ben; Zhang, Zhen; Kurman, Robert J; Eberhart, Charles G; Shih, Ie Ming; Wang, Tian-Li.

In: Cancer Research, Vol. 66, No. 12, 15.06.2006, p. 6312-6318.

Research output: Contribution to journalArticle

Park JT, Li M, Nakayama K, Mao TL, Davidson B, Zhang Z et al. Notch3 gene amplification in ovarian cancer. Cancer Research. 2006 Jun 15;66(12):6312-6318. https://doi.org/10.1158/0008-5472.CAN-05-3610
Park, Joon T. ; Li, Mei ; Nakayama, Kentaro ; Mao, Tsui Lien ; Davidson, Ben ; Zhang, Zhen ; Kurman, Robert J ; Eberhart, Charles G ; Shih, Ie Ming ; Wang, Tian-Li. / Notch3 gene amplification in ovarian cancer. In: Cancer Research. 2006 ; Vol. 66, No. 12. pp. 6312-6318.
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