Upregulation of Notch pathway molecules in oral squamous cell carcinoma

Upregulation of Notch pathway molecules in oral squamous cell carcinoma
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DOI:
10.3892/ijo_00000558
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发表时间:
2010-04-01
影响因子:
5.2
通讯作者:
Nakamura, Norifumi
Nakamura, Norifumi
中科院分区:
医学2区
文献类型:
--
作者:
Hijioka, Hiroshi;Setoguchi, Takao;Nakamura, Norifumi

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Notch途径的组成性激活已在各种类型的恶性肿瘤中得到证实。然而,Notch通路如何参与口腔鳞状细胞癌(OSCC)的发病机制仍不清楚。我们研究了Notch通路分子在OSCC细胞系和活检标本中的表达,并检查了Notch通路抑制的效果。逆转录-聚合酶链反应显示Notch 1、Notch 2表达上调。Jagged 1、HES 1和HEY 1在OSCC细胞系和活检标本中的表达。免疫组化结果显示,Notch胞内结构域在口腔鳞癌细胞系和活检标本中均聚集于细胞核内。此外,Jagged 1在OSCC细胞系和活检标本的细胞质中表达。此外。使用γ-分泌酶抑制剂抑制Notch途径可防止体外OSCC的生长。这些研究结果表明,抑制Notch途径抑制OSCC的生长,可能是一种有用的方法,用于治疗OSCC患者。
The constitutive activation of the Notch pathway has been demonstrated in various types of malignancies. However, it remains unclear how the Notch pathway is involved in the pathogenesis of oral squamous cell carcinoma (OSCC). We investigated the expression of Notch pathway molecules in OSCC cell lines and biopsy specimens and examined the effect of Notch pathway inhibition. Reverse transcription-polymerase chain reaction revealed upregulation of Notch1, Notch2. Jagged1, HES1 and HEY1 in both OSCC cell lines and biopsy specimens. Immunohistochemical examination showed that the Notch intracellular domain accumulates in the nucleus of cells in OSCC cell lines and biopsy specimens. In addition, Jagged1 is expressed in the cytoplasm of cells in OSCC cell lines and biopsy specimens. Furthermore. Notch pathway inhibition using a gamma-secretase inhibitor prevented the growth of OSCC in vitro. These findings suggest that inhibition of the Notch pathway suppresses OSCC growth and may be a useful approach for the treatment of patients with OSCC.