TY - JOUR
T1 - Upregulated expression of ADAM12 is associated with progression of oral squamous cell carcinoma
AU - Uehara, Erika
AU - Shiiba, Masashi
AU - Shinozuka, Keiji
AU - Saito, Kengo
AU - Kouzu, Yukinao
AU - Koike, Hirofumi
AU - Kasamatsu, Atsushi
AU - Sakamoto, Yosuke
AU - Ogawara, Katsunori
AU - Uzawa, Katsuhiro
AU - Tanzawa, Hideki
PY - 2012/5
Y1 - 2012/5
N2 - 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)-β3 expression. Our data indicate that ADAM12 is overexpressed in OSCC and might accelerate cellular proliferation. Its function may be associated with TGF-β 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.
AB - 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)-β3 expression. Our data indicate that ADAM12 is overexpressed in OSCC and might accelerate cellular proliferation. Its function may be associated with TGF-β 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.
KW - (a) disintegrin and metalloproteinases
KW - Oral squamous cell carcinoma
KW - Transforming growth factor β3
UR - http://www.scopus.com/inward/record.url?scp=84860307089&partnerID=8YFLogxK
U2 - 10.3892/ijo.2012.1339
DO - 10.3892/ijo.2012.1339
M3 - Article
C2 - 22267082
AN - SCOPUS:84860307089
SN - 1019-6439
VL - 40
SP - 1414
EP - 1422
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 5
ER -
