Expression and role of anion exchanger 1 in esophageal squamous cell carcinoma.
Recent studies have described important roles for the anion exchanger (AE) in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AE1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. AE1 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its distribution pattern was related to the histological degree of the differentiation of SCC or the pT category. Among patients with pT2-3 ESCC, the 5-year survival rate of patients with diffuse AE1 expression (40.2%) was significantly lower than that of patients with focal expression (74.0%). AE1 was strongly expressed in KYSE150 and TE8 human ESCC cells. The depletion of AE1 using siRNA inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that MAPK and Hedgehog signaling pathway-related genes, such as DHH, and GLI1, were down-regulated in AE1-depleted KYSE150 cells. In conclusions, the results of the present study suggest that the diffuse expression of AE1 is related to a worse prognosis in patients with advanced ESCC, and that it regulates tumor progression by affecting MAPK and Hedgehog signaling pathways. These results provide an insight into the role of AE1 as a mediator of and/or a biomarker for ESCC.
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Atsushi
A
Shiozaki
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Michihiro
M
Kudou
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Daisuke
D
Ichikawa
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Hiroki
H
Shimizu
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Tomohiro
T
Arita
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Toshiyuki
T
Kosuga
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Hirotaka
H
Konishi
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Shuhei
S
Komatsu
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Hitoshi
H
Fujiwara
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Kazuma
K
Okamoto
Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Mitsuo
M
Kishimoto
Department of Molecular Cell Physiology and Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.|Japan Institute for Food Education and Health, St. Agnes' University, Kyoto, 602-8013, Japan.
Yoshinori
Y
Marunaka
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
Eigo
E
Otsuji
D000368:Aged; D001457:Anion Exchange Protein 1, Erythrocyte / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000077277:Esophageal Squamous Cell Carcinoma; D016629:Esophagectomy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015996:Survival Rate; D000071676:Zinc Finger Protein GLI1 / Q000096:biosynthesis
D001457:Anion Exchange Protein 1, Erythrocyte; D014408:Biomarkers, Tumor; C509245:DHH protein, human; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D034741:RNA, Small Interfering; D000071676:Zinc Finger Protein GLI1
AE1; Hedgehog signaling pathway; MAPK; cellular physiology; esophageal squamous cell carcinoma