title: Tripeptidyl peptidase II in human oral squamous cell carcinoma.
abstract: OBJECTIVE
  Tripeptidyl peptidase II (TPP2), a member of the family of eukaryotic serine peptidase, has been implicated in DNA repair, cellular division, and apoptosis. The aim of this study was to examine TPP2 expression and its functional mechanisms in oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  TPP2 mRNA and protein expression in seven OSCC-derived cells (Ca9-22, HSC-2, HSC-3, HSC-4, HO-1-N-1, H1, and Sa3) was analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Since previous studies indicated that TPP2 might control chromosomal division, we investigated cellular proliferation and spindle assembly checkpoint (SAC) molecules, MAD2 and CCNB1. In addition, we evaluated the correlation between TPP2 expression levels in primary OSCCs (n = 108 specimens) and the clinicopathologic status by immunohistochemistry (IHC).
  
  
  RESULTS
  TPP2 mRNA and protein were significantly (P < 0.05) up-regulated in OSCC-derived cells compared with human normal oral keratinocytes. Suppression of TPP2 expression with shRNA significantly (P < 0.05) inhibited cellular proliferation compared with the control cells. In addition, appropriate localization of MAD2 and up-regulation of CCNB1 were observed in TPP2 knockdown OSCC cells. IHC showed that TPP2 expression in primary OSCCs was significantly (P < 0.001) greater than that in the normal oral counterparts, and the TPP2-positive cases were significantly (P < 0.05) correlated with tumor size.
  
  
  CONCLUSIONS
  The current study showed that overexpression of TPP2 occurs frequently during oral carcinogenesis and might be associated with OSCC progression via SAC activation.
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Usukura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okamoto
authors.forename: Yukinao
authors.initials: Y
authors.lastname: Kouzu
authors.forename: Morihiro
authors.initials: M
authors.lastname: Higo
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Koike
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ogawara
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
mesh_terms: D000368:Aged; D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D015151:Immunoblotting; D007564:Japan; D008207:Lymphatic Metastasis; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
chemical_list: C534699:CCNB1 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056744:Cyclin B1; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases