Siah-1 is associated with expression of hypoxia-inducible factor -l alpha in oral squamous cell carcinoma

作者：Aga Mitsuharu; Kondo Satoru; Wakisaka Naohiro; Moriyama Kita Makiko; Endo Kazuhira; Nakanishi Yosuke; Murono Shigeyuki; Sugimoto Hisashi; Ueno Takayoshi; Yoshizaki Tomokazu^*

来源：Auris Nasus Larynx, 2017, 44(2): 213-219.

DOI：10.1016/j.an1.2016.06.007

• Siah-1
• HIF-l alpha
• Oral squamous cell carcinoma

Objective: Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of the HIF-1 alpha and HIF-1 beta subunits. HIF-1 is a central regulator of responses to hypoxia; it enhances metastasis-related factors such as matrix metalloproteinases and vascular endothelial growth factor (VEGF). We have reported critical roles for HEF-l alpha in tumor microenvironments, and oncogenic properties of la have been suggested in malignancies. Seven in absentia homologue (Siah) appeared to upregulate HIF-1 production, which prompted us to investigate the Siah association with HIF-1 a expression in oral squamous cell carcinoma (OSCC).
Methods: Samples from fifty-five patients with OSCC were evaluated by immunohistochemistry for the protein expressions of Siah-1 and -2, HIF-1 alpha, and VEGF. The expression levels of each protein and clinicopathological data were statistically analyzed.
Results: Siah-1 and, Siah-2, HIF-l alpha, and VEGF were immunolocalized on the cell membranes and cytoplasm of the tumor cells. The expression of Siah-1 showed a linear dependence on the expression of HIF-1 a (r = 0.627,p p < 0.001). In 17 cases of the large tumor size category (T3 and 4), the mean Siah-1 expression score was significantly higher than in 41 cases of the small tumor size category (T1 and 2; p = 0.001). In addition, in 16 cases of the lymph node metastasis-positive category (N1-3), the mean Siah-1 expression score was significantly higher than that in 42 cases of the lymph node metastasis-negative category (N0, p = 0.001).
Conclusion: These results suggested that the expressions of Siah-1 and HIF-l alpha were clearly correlated in OSCC. Moreover, Siah-1 appears to be correlated with clinicopathological data, particularly tumor size.

• 出版日期2017-4