Increase of disintergin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma.
The A disintergin and metalloprotease (ADAM) superfamilies play important roles in angiogenesis, development, and tumorigenesis. Amyloid precursor protein (APP) is an important protein related to Alzheimer's disease. Recent research shows that ADAM10 alpha-secretase activity can release the secreted form of APP. We have previously demonstrated an increase of APP expression in oral squamous cell carcinoma (OSCC) and related OSCC cell lines. The present study characterizes ADAM10 expression in the neoplastic process of OSCC. RT-PCR analysis revealed a two-fold increase in APP mRNA expression in 50% of OSCC (n=50) relative to corresponding non-malignant matched tissues (NMMT). This increase in mRNA expression occurred at the preneoplastic stage. A significant correlation between mRNA expression of ADAM10 and APP in OSCC was noted. A non-buccal subset of OSCC correlated with an increase of mRNA expression of both ADAM10 and APP. The increase of ADAM10 protein expression in the majority of OSCC tissues and cell lines studies was confirmed by Western blot analysis. Additionally, an increase of ADAM10 immunoreactivity in OSCC relative to NMMT was noted. An antisense oligonucleotide against ADAM10 reduced ADAM10 expression as well as growth in an OSCC cell line. However, this treatment did not reduce the secreted form APP. This study suggests that ADAM10 expression plays a role in the carcinogenesis of OSCC and proliferation of OSCC cells, independent of APP processing.
Ko
Shun-Yao
SY
School of Dentistry, National Yang-Ming University, Li-Nong St., Sec., 2, No 155, Taipei 112, Taiwan, ROC.
Lin
Shu-Chun
SC
Wong
Yong-Kie
YK
Liu
Chung-Ji
CJ
Chang
Kuo-Wei
KW
Liu
Tsung-Yun
TY
D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000072197:ADAM10 Protein; D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human