TY - JOUR
T1 - The significance of PITX2 overexpression in human colorectal cancer
AU - Hirose, Hajime
AU - Ishii, Hideshi
AU - Mimori, Koshi
AU - Tanaka, Fumiaki
AU - Takemasa, Ichiro
AU - Mizushima, Tsunekazu
AU - Ikeda, Masataka
AU - Yamamoto, Hirofumi
AU - Sekimoto, Mitsugu
AU - Doki, Yuichiro
AU - Mori, Masaki
N1 - Funding Information:
ACKNOWLEDGMENT We thank Dr. Miyoshi, Dr. Kim, Dr. Okano, and Dr. Uemura for their excellent advice and technical assistance. This work was supported in part by a grant from Core Research for Evolutional Science and Technology (CREST), a Grant-in-Aid for Scientific Research on Priority Areas (20012039), Grants-in-Aid for Scientific Research (S: 21229015 and C: 20590313) from the Ministry of Education, Culture, Sports, Science, and Technology, and a grant from the Tokyo Biochemical Research Foundation, Japan.
PY - 2011/10
Y1 - 2011/10
N2 - Purpose: The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC). Although PITX2 is reportedly involved in various functions, including tissue development by controlling cell growth, its significance in CRC remains unclear. We report our findings regarding abnormal PITX2 expression in human CRC. Methods: PITX2 expression was evaluated in 5 human CRC cell lines and 92 primary CRC samples. Cell growth was evaluated after inhibition of PITX2 expression or after exogenous introduction of PITX2. Results: PITX2 expression was seen in all the five CRC cell lines. The study of tissue samples indicated that PITX2 expression was significantly higher in cancerous tissue than in paired control tissue (P = 0.0471). Patients with lower PITX2 expression showed a poorer overall survival rate than those with higher PITX2 expression (P = 0.0481). Multivariate analysis demonstrated that PITX2 expression was an independent prognostic factor. Experimental knockdown and introduction of PITX2 also demonstrated that the level of PITX2 expression is inversely associated with cell growth and invasion in vitro. Conclusions: PITX2 expression is significantly related to the biological behavior of CRC cells and appears to be correlated with clinical survival. Thus, this study revealed a previously uncharacterized unique role and significance of PITX2 expression in CRC.
AB - Purpose: The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC). Although PITX2 is reportedly involved in various functions, including tissue development by controlling cell growth, its significance in CRC remains unclear. We report our findings regarding abnormal PITX2 expression in human CRC. Methods: PITX2 expression was evaluated in 5 human CRC cell lines and 92 primary CRC samples. Cell growth was evaluated after inhibition of PITX2 expression or after exogenous introduction of PITX2. Results: PITX2 expression was seen in all the five CRC cell lines. The study of tissue samples indicated that PITX2 expression was significantly higher in cancerous tissue than in paired control tissue (P = 0.0471). Patients with lower PITX2 expression showed a poorer overall survival rate than those with higher PITX2 expression (P = 0.0481). Multivariate analysis demonstrated that PITX2 expression was an independent prognostic factor. Experimental knockdown and introduction of PITX2 also demonstrated that the level of PITX2 expression is inversely associated with cell growth and invasion in vitro. Conclusions: PITX2 expression is significantly related to the biological behavior of CRC cells and appears to be correlated with clinical survival. Thus, this study revealed a previously uncharacterized unique role and significance of PITX2 expression in CRC.
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U2 - 10.1245/s10434-011-1653-z
DO - 10.1245/s10434-011-1653-z
M3 - Article
C2 - 21479692
AN - SCOPUS:80052738633
SN - 1068-9265
VL - 18
SP - 3005
EP - 3012
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 10
ER -
