Increased expression of amyloid precursor protein in oral squamous cell carcinoma.
In our previous study, we identified amyloid precursor protein (APP) in an oral squamous cell carcinoma (OSCC)-enriching subtractive hybridization library. Our present study attempts to define the significance of APP expression in the genesis of OSCC. RT-PCR analysis showed increase in APP mRNA expression for more than 2-fold in 76% of OSCC (n = 55) relative to corresponding non-cancerous matched tissues (NCMT). The majority of esophageal SCCs also had increase in APP mRNA expression. OSCC patients exhibiting increase in APP mRNA expression had significantly lower survival rate compared to patients exhibiting the opposite status. Western blotting analysis identified APP751 and APP770 as the major APP isoforms in oral keratinocytes. A high correlation between mRNA and protein expressions of APP was noted in OSCC/NCMT pairs. Immunohistochemistry further showed a remarkable increase of APP in OSCC tissue relative to NCMT. Treatment with an antisense oligonucleotide against APP reduced cellular and secreted APP as well as growth in an OSCC cell line. Our study provides novel clues that APP expression is involved in the proliferation and carcinogenesis of OSCC. Correlated with such pathogenesis was the survival of its victims. The degree of APP expression could serve as an invaluable marker for oral carcinogenesis.
Ko
Shun-Yao
SY
Institute of Pharmacology National Yang-Ming University, Taiwan.
Lin
Shu-Chun
SC
Chang
Kuo-Wei
KW
Wong
Yong-Kie
YK
Liu
Chung-Ji
CJ
Chi
Chin-Wen
CW
Liu
Tsung-Yun
TY
D000328:Adult; D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000503:physiopathology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000503:physiopathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D014408:Biomarkers, Tumor; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger