Upregulated expression of ADAM12 is associated with progression of oral squamous cell carcinoma

被引:17
作者
Uehara, Erika [2 ]
Shiiba, Masashi [1 ]
Shinozuka, Keiji [3 ]
Saito, Kengo [4 ]
Kouzu, Yukinao [3 ]
Koike, Hirofumi [3 ]
Kasamatsu, Atsushi
Sakamoto, Yosuke
Ogawara, Katsunori
Uzawa, Katsuhiro [3 ]
Tanzawa, Hideki [3 ]
机构
[1] Chiba Univ Hosp, Div Dent & Oral Maxillofacial Surg, Chuo Ku, Chiba 2608677, Japan
[2] Chiba Univ, Sch Med, Chuo Ku, Chiba 2608670, Japan
[3] Chiba Univ, Grad Sch Med, Dept Clin Mol Biol, Chiba 2608670, Japan
[4] Chiba Univ, Grad Sch Med, Dept Mol Virol, Chiba 2608670, Japan
关键词
oral squamous cell carcinoma; (a) disintegrin and metalloproteinases; transforming growth factor beta 3; TGF-BETA; SELECTIVE-INHIBITION; TUMOR PROGRESSION; MELTRIN-ALPHA; DISINTEGRIN; GROWTH; DOMAIN; PROTEIN; CANCER; SRC;
D O I
10.3892/ijo.2012.1339
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
ADAMs are a disintegrin and metalloproteinase family of membrane-associated metalloproteinases characterized by their multidomain structure, and have been reported to be associated with various malignant tumors. The aim of this study was to identify crucial members of the ADAM family in oral squamous cell carcinoma (OSCC), and to reveal their biological function and clinical significance. To clarify whether ADAM family genes are involved in OSCC, changes in the expression profile were investigated by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis and immunohistochemical analysis. Functional analysis was performed by comparing cellular proliferation of siADAM-transfected cell lines and parental cell lines. Real-time qRT-PCR analysis identified significantly upregulated expression of ADAM12 in OSCC-derived cell lines. This was validated in OSCC samples using real-time qRT-PCR and immunohistochemical staining. ADAM12 expression was correlated with TNM classification; significantly greater expression of ADAM12 was observed in tumors with higher T classification and more advanced stages. Moreover, siADAM12-transfected cells showed both a suppressed proliferation rate and increased transforming growth factor (TGF)-1 beta 3 expression. Our data indicate that ADAM12 is overexpressed in OSCC and might accelerate cellular proliferation. Its function may be associated with TGF-beta signaling. This study suggests that controlling the expression or activity of ADAM12 could be a useful strategy in the development of an effective cure for OSCC.
引用
收藏
页码:1414 / 1422
页数:9
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