Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma.
The partition-defective 3 (PAR-3) protein is implicated in the formation of tight junctions at epithelial cell-cell contacts. We investigated DNA copy number aberrations in human esophageal squamous cell carcinoma (ESCC) cell lines using a high-density oligonucleotide microarray and found a homozygous deletion of PARD3 (the gene encoding PAR-3). Exogenous expression of PARD3 in ESCC cells lacking this gene enhanced the recruitment of zonula occludens 1 (ZO-1), a marker of tight junctions, to sites of cell-cell contact. Conversely, knockdown of PARD3 in ESCC cells expressing this gene caused a disruption of ZO-1 localization at cell-cell borders. A copy number loss of PARD3 was observed in 15% of primary ESCC cells. Expression of PARD3 was significantly reduced in primary ESCC tumors compared with their nontumorous counterparts, and this reduced expression was associated with positive lymph node metastasis and poor differentiation. Our results suggest that deletion and reduced expression of PARD3 may be a novel mechanism that drives the progression of ESCC.
Zen
K
K
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
Yasui
K
K
Gen
Y
Y
Dohi
O
O
Wakabayashi
N
N
Mitsufuji
S
S
Itoh
Y
Y
Zen
Y
Y
Nakanuma
Y
Y
Taniwaki
M
M
Okanoue
T
T
Yoshikawa
T
T
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006720:Homozygote; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D007365:Intercellular Junctions / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D062826:Zonula Occludens-1 Protein
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C509689:PARD3 protein, human; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein