Upregulation of Notch pathway molecules in oral squamous cell carcinoma

• Published in: International journal of oncology Vol. 36; no. 4; pp. 817 - 822
• Main Authors: HIJIOKA, Hiroshi, SETOGUCHI, Takao, MIYAWAKI, Akihiko, HUI GAO, ISHIDA, Takayuki, KOMIYA, Setsuro, NAKAMURA, Norifumi
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.04.2010
• Subjects: Aged; Amyloid Precursor Protein Secretases - antagonists & inhibitors; Amyloid Precursor Protein Secretases - metabolism; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological and medical sciences; Biopsy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Female; Homeodomain Proteins - metabolism; Humans; Immunohistochemistry; Medical sciences; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Otorhinolaryngology. Stomatology; Protease Inhibitors - pharmacology; Receptor, Notch1 - metabolism; Receptor, Notch2 - metabolism; Receptors, Notch - genetics; Receptors, Notch - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Signal Transduction - genetics; Time Factors; Transcription Factor HES-1; Tumors; Up-Regulation; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Notch receptor; Cancerology; Oral cancer; Stomatology; Notch; Oral cavity disease; Inhibitor; Malignant tumor; Oral squamous cell carcinoma; γ-secretase inhibitor; Cancer
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo_00000558

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.