| RRC ID |
45470
|
| 著者 |
Sakamoto K, Imai K, Higashi T, Taki K, Nakagawa S, Okabe H, Nitta H, Hayashi H, Chikamoto A, Ishiko T, Beppu T, Baba H.
|
| タイトル |
Significance of P-cadherin overexpression and possible mechanism of its regulation in intrahepatic cholangiocarcinoma and pancreatic cancer.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
It has become evident that P-cadherin, one of the classical cadherins, contributes to the malignant behavior of several types of cancer. In this study, we analyzed the expression of P-cadherin and its clinicopathological and prognostic values in intrahepatic cholangiocarcinoma (ICC) and pancreatic cancer. Furthermore, we investigated the functional role of P-cadherin in these cancer cells by knockdown and overexpression in vitro and by analyzing the correlation between the P-cadherin expression and its promoter methylation status. Thirty of 59 ICC cases (51%) and 36 of 73 pancreatic cancer cases (49%) stained positive for P-cadherin with mainly membranous distribution in tumor cells by immunohistochemistry. P-cadherin expression was significantly correlated with several clinicopathological factors, which reflect tumor behavior, and was identified as an independent adverse prognostic factor for disease-free survival in patients with ICC (relative risk [RR] 2.93, P = 0.04) and pancreatic cancer (RR 2.68, P = 0.005) via multivariate analyses. P-cadherin downregulation by siRNA suppressed migration and invasion, and P-cadherin overexpression induced the opposite effects in both ICC and pancreatic cancer cells, without any effects on cell proliferation. P-cadherin expression was related to its promoter methylation status in both cell lines and cancer tissues. In summary, P-cadherin overexpression may serve as a useful biomarker of invasive phenotype and poor prognosis; P-cadherin expression was found to be regulated by its promoter methylation. These results suggest that P-cadherin represents a novel therapeutic target for the treatment of ICC and pancreatic cancer.
|
| 巻・号 |
106(9)
|
| ページ |
1153-62
|
| 公開日 |
2015-9-1
|
| DOI |
10.1111/cas.12732
|
| PMID |
26132727
|
| PMC |
PMC4582984
|
| MeSH |
Aged
Bile Duct Neoplasms / genetics*
Bile Duct Neoplasms / pathology*
Biomarkers, Tumor / genetics
Cadherins / genetics*
Cell Line, Tumor
Cell Proliferation / genetics
Cholangiocarcinoma / genetics*
Cholangiocarcinoma / pathology*
Disease-Free Survival
Down-Regulation / genetics
Female
Gene Expression Regulation, Neoplastic / genetics
Humans
Male
Pancreatic Neoplasms / genetics*
Pancreatic Neoplasms / pathology*
Prognosis
Promoter Regions, Genetic / genetics
|
| IF |
4.966
|
| 引用数 |
6
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RBE(RCB1292)
SSP-25(RCB1293)
YSCCC(RCB1549)
PANC-1(RCB2095)
PK-8(RCB2700)
PK-59(RCB1901)
KLM-1(RCB2138)
MIA Paca2(RCB2094) |
