PMID- 15027119
OWN - NLM
STAT- MEDLINE
DCOM- 20040506
LR  - 20211203
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 109
IP  - 6
DP  - 2004 May 10
TI  - Role for dipeptidyl peptidase IV in tumor suppression of human non small cell 
      lung carcinoma cells.
PG  - 855-66
AB  - Lung cancer is the leading cause of cancer death. Lung cancers produce a variety 
      of mitogenic growth factors that stimulate tumor cell proliferation and 
      migration. The cell surface protease, dipeptidyl peptidase IV (DPPIV), is 
      involved in diverse biologic functions, including peptide-mediated cellular 
      growth and differentiation. DPPIV is expressed in various normal tissues, 
      including lung tissue, and its expression is lost in many types of human cancers. 
      DPPIV expression and its enzymatic activity are detected in normal bronchial and 
      alveolar epithelium but different histologic subtypes of lung carcinomas lose 
      DPPIV expression. To investigate the role of DPPIV in lung carcinoma, we examined 
      the expression of DPPIV at both mRNA and protein levels in non small cell lung 
      cancer (NSCLC) cell lines and normal human bronchial epithelial cells. DPPIV 
      expression was detectable in normal lung epithelial cells, but was absent or 
      markedly reduced in all NSCLC cell lines at both mRNA and protein levels. 
      Restoration of DPPIV expression in NSCLC cells resulted in profound morphologic 
      changes, inhibition of cell proliferation, anchorage-independent growth, in vitro 
      cell migration and tumorigenicity in nude mice. DPPIV reexpression also 
      correlated with increased p21 expression, leading to induction of apoptosis and 
      cell cycle arrest in G1 stage. These effects were accompanied by increased 
      expression of cell surface proteins, fibroblast-activating protein (Fapalpha) and 
      CD44 that are associated with suppression of tumor growth and metastasis. Thus, 
      DPPIV functions as a tumor suppressor, and its downregulation may contribute to 
      the loss of growth control in NSCLC cells.
CI  - Copyright 2004 Wiley-Liss, Inc.
FAU - Wesley, Umadevi V
AU  - Wesley UV
AD  - Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, 
      NY, USA. uwesley@zoo.uvm.edu
FAU - Tiwari, Shakuntala
AU  - Tiwari S
FAU - Houghton, Alan N
AU  - Houghton AN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cdkn1a protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.- (fibroblast activation protein alpha)
RN  - EC 3.4.24.- (Gelatinases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Carcinoma, Non-Small-Cell Lung/*enzymology/pathology
MH  - Cell Adhesion
MH  - Cell Movement
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/metabolism
MH  - Dipeptidyl Peptidase 4/*genetics/*metabolism
MH  - Down-Regulation
MH  - Endopeptidases
MH  - *Gelatinases
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Enzymologic/*physiology
MH  - Humans
MH  - Hyaluronan Receptors/metabolism
MH  - In Situ Nick-End Labeling
MH  - Lung Neoplasms/*enzymology/pathology
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Mutation
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/metabolism
MH  - Serine Endopeptidases/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2004/03/18 05:00
MHDA- 2004/05/07 05:00
CRDT- 2004/03/18 05:00
PHST- 2004/03/18 05:00 [pubmed]
PHST- 2004/05/07 05:00 [medline]
PHST- 2004/03/18 05:00 [entrez]
AID - 10.1002/ijc.20091 [doi]
PST - ppublish
SO  - Int J Cancer. 2004 May 10;109(6):855-66. doi: 10.1002/ijc.20091.