Expression of MUC1 in Human Squamous Cell Carcinoma of the Oral Cavity
Masakatsu Fukuda PhD, Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University, School of Dentistry, Sakado, Japan
Syota Takizawa Ph.D., Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University, School of Dentistry, Sakado, Japan
Yukihiro Kawamoto PhD, Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University, School of Dentistry, Sakado, Japan
Yoshito Ohyama PhD, Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University, School of Dentistry, Sakado, Japan
Katsuyuki Inoue PhD, Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University, School of Dentistry, Sakado, Japan
Seiji Suzuki Ph.D., Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University, School of Dentistry, Sakado, Japan
Hideaki Sakashita Ph.D., Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University, School of Dentistry, Sakado, Japan
Objective: Mucins, large extracellular proteins that are heavily glycosylated with complex oligosaccharides, establish a selective molecular barrier at the epithelial surface and engage in morphogenetic signal transduction. Alterations in mucin expression or glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion and immune surveillance. Furthermore, association of MUC1 with p53 in cancer results in inhibition of p53-mediated apoptosis and promotion of p53-mediated cell cycle arrest. In addition, increased expression of MUC1 in cancer cells that promotes cancer cell invasion through beta-catenin, resulting in the initiation of epithelial-mesenchymal transition which promotes the formation of metastases. However, little data are available regarding the role of MUC1 in oral cancers. Then, this study examined the impact of MUC1 against oral squamous cell carcinoma.
Materials and Methods: Five human oral squamous cell carcinoma (HOSCC) cell lines, HSC-2, HSC-3, HSC-4, Ca9-22 and SAS, were used in this study. Caspase activity was determined by Caspase-Glo. We measured the expression of MUC1 mRNA and protein by RT-PCR and Western blotting in oral cancer cells, respectively. Morphological change was observed by light microscopy.
Results: It was demonstrated that MUC1 mRNA and protein certainly expressed on 5 oral cancer cells. As a result of real time qRT-PCR, MUC1 expression level was the highest in HSC-4 cells. MUC1 knockdown with MUC1 siRNA in HSC-4 cells revealed to decrease the number of HSC-4 cells. Caspase activity was also determined. Expression of MUC1 was increased in the hypoxia condition. We observed concomitant increase of HIF-1alpha and MUC1 in HSC-4 cells.
Conclusion: These findings suggested that MUC1 might serve as a potential therapeutic target in HOSCC.
References:
1. Sébastien Aubert, Valérie Fauquette, Brigitte Hémon, et al. : MUC1, a New Hypoxia Inducible Factor Target Gene, Is an Actor in Clear Renal Cell Carcinoma Tumor Progression. Cancer Res 69: 5707-5715, 2009.
2. Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer 4: 45-60, 2004.
