XB130 as an independent prognostic factor in human esophageal squamous cell carcinoma.
BACKGROUND
Adaptor proteins, with multimodular structures, can participate in the regulation of various cellular functions. A novel adaptor protein XB130 has been implicated as a substrate and regulator of tyrosine kinase-mediated signaling and in controlling cell proliferation and apoptosis in thyroid and lung cancer cells. However, its expression and role in gastrointestinal cancer have not been investigated. We sought to determine the role of XB130 in cell cycle progression of esophageal squamous cell carcinoma (ESCC) cells and to examine its expression and effects on the prognosis of patients with ESCC.


METHODS
Expression of XB130 in human ESCC cell lines was analyzed by Western blot testing and immunofluorescent staining. Knockdown experiments with XB130 small interfering RNA (siRNA) were conducted, and the effect on cell cycle progression was analyzed. Immunohistochemistry of XB130 for 52 primary tumor samples obtained from patients with ESCC undergoing esophagectomy was performed.


RESULTS
XB130 was highly expressed in TE2, TE5, and TE9 cells. In these cells, knockdown of XB130 with siRNA inhibited G1-S phase progression and increased the expression of p21, the cyclin-dependent kinase inhibitor. Immunohistochemistry showed that 71.2% of the patients expressed XB130 in the nuclei and/or cytoplasm of the ESCC cells. Further, nuclear expression of XB130 was an independent prognostic factor of postoperative survival.


CONCLUSIONS
These observations suggest that the expression of XB130 in ESCC cells may affect cell cycle progression and impact prognosis of patients with ESCC. A deeper understanding of XB130 as a mediator and/or biomarker in ESCC is needed.
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. shiozaki@koto.kpu-m.ac.jp
Atsushi
A
Shiozaki
Toshiyuki
T
Kosuga
Daisuke
D
Ichikawa
Shuhei
S
Komatsu
Hitoshi
H
Fujiwara
Kazuma
K
Okamoto
Daisuke
D
Iitaka
Shingo
S
Nakashima
Hiroki
H
Shimizu
Takeshi
T
Ishimoto
Maki
M
Kitagawa
Yoshito
Y
Nakou
Mitsuo
M
Kishimoto
Mingyao
M
Liu
Eigo
E
Otsuji
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D016629:Esophagectomy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
C521126:AFAP1L2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering