TY - JOUR
T1 - The role of Pea3 group transcription factors in esophageal squamous cell carcinoma
AU - Yuen, Hiu Fung
AU - McCrudden, Cian M.
AU - Chan, Ka Kui
AU - Chan, Yuen Piu
AU - Wong, Michelle Lok Yee
AU - Chan, Kelvin Yuen Kwong
AU - Khoo, Ui Soon
AU - Law, Simon
AU - Srivastava, Gopesh
AU - Lappin, Terence R.
AU - Chan, Kwok Wah
AU - El-Tanani, Mohamed
N1 - Funding Information:
Supported by a postdoctoral fellowship from Cancer Research UK (H.-F.Y.).
PY - 2011/8
Y1 - 2011/8
N2 - The transcription factors Pea3, Erm, and Er81 can promote cancer initiation and progression in various types of solid tumors. However, their role in esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we found that the expression levels of Pea3 and Erm, but not that of Er81, were significantly higher in ESCC compared with nontumor esophageal epithelium. A high level of Pea3 expression was significantly correlated with a shorter overall survival in a cohort of 81 patients with ESCC and the subgroup with N1 stage tumor (Wilcoxon-Gehan test, P = 0.016 and P = 0.001, respectively). Pea3 was overexpressed in seven ESCC cell lines compared with two immortalized esophageal cell lines. Pea3 knockdown reduced cell proliferation and suppressed nonadherent growth, migration, and invasion in ESCC cells in vitro. In addition, Pea3 knockdown in ESCC cells resulted in a down-regulation of phospho-Akt and matrix metalloproteinase 13, whereas a significant positive correlation in the expression levels was observed between Pea3 and phospho-Akt (r = 0.281, P < 0.013) and between Pea3 and matrix metalloproteinase 13 in the human specimens (r = 0.462, P < 0.001). Moreover, Pea3 modulated the sensitivity of EC109 cells to doxorubicin, probably via reduced activity of the phosphatidylinositol 3-kinaseAktmammalian target of Rapamycin complex 1 pathway on Pea3 knockdown. In conclusion, our results suggest that Pea3 plays an important role in the progression of ESCC.
AB - The transcription factors Pea3, Erm, and Er81 can promote cancer initiation and progression in various types of solid tumors. However, their role in esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we found that the expression levels of Pea3 and Erm, but not that of Er81, were significantly higher in ESCC compared with nontumor esophageal epithelium. A high level of Pea3 expression was significantly correlated with a shorter overall survival in a cohort of 81 patients with ESCC and the subgroup with N1 stage tumor (Wilcoxon-Gehan test, P = 0.016 and P = 0.001, respectively). Pea3 was overexpressed in seven ESCC cell lines compared with two immortalized esophageal cell lines. Pea3 knockdown reduced cell proliferation and suppressed nonadherent growth, migration, and invasion in ESCC cells in vitro. In addition, Pea3 knockdown in ESCC cells resulted in a down-regulation of phospho-Akt and matrix metalloproteinase 13, whereas a significant positive correlation in the expression levels was observed between Pea3 and phospho-Akt (r = 0.281, P < 0.013) and between Pea3 and matrix metalloproteinase 13 in the human specimens (r = 0.462, P < 0.001). Moreover, Pea3 modulated the sensitivity of EC109 cells to doxorubicin, probably via reduced activity of the phosphatidylinositol 3-kinaseAktmammalian target of Rapamycin complex 1 pathway on Pea3 knockdown. In conclusion, our results suggest that Pea3 plays an important role in the progression of ESCC.
UR - http://www.scopus.com/inward/record.url?scp=80052485012&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2011.04.004
DO - 10.1016/j.ajpath.2011.04.004
M3 - Article
C2 - 21689625
AN - SCOPUS:80052485012
SN - 0002-9440
VL - 179
SP - 992
EP - 1003
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -
