RRC ID |
69445
|
Author |
Yamato I, Sho M, Shimada K, Hotta K, Ueda Y, Yasuda S, Shigi N, Konishi N, Tsujikawa K, Nakajima Y.
|
Title |
PCA-1/ALKBH3 contributes to pancreatic cancer by supporting apoptotic resistance and angiogenesis.
|
Journal |
Cancer Res
|
Abstract |
The PCA-1/ALKBH3 gene implicated in DNA repair is expressed in several human malignancies but its precise contributions to cancer remain mainly unknown. In this study, we have determined its functions and clinical importance in pancreatic cancer. PCA-1/ALKBH3 functions in proliferation, apoptosis and angiogenesis were evaluated in human pancreatic cancer cells in vitro and in vivo. Further, PCA-1/ALKBH3 expression in 116 patients with pancreatic cancer was evaluated by immunohistochemistry. siRNA-mediated silencing of PCA-1/ALKBH3 expression induced apoptosis and suppressed cell proliferation. Conversely, overexpression of PCA-1/ALKBH3 increased anchorage-independent growth and invasiveness. In addition, PCA-1/ALKBH3 silencing downregulated VEGF expression and inhibited angiogenesis in vivo. Furthermore, immunohistochemical analysis showed that PCA-1/ALKBH3 expression was abundant in pancreatic cancer tissues, where it correlated with advanced tumor status, pathological stage and VEGF intensity. Importantly, patients with low positivity of PCA-1/ALKBH3 expression had improved postoperative prognosis compared with those with high positivity. Our results establish PCA-1/ALKBH3 as important gene in pancreatic cancer with potential utility as a therapeutic target in this fatal disease.
|
Volume |
72(18)
|
Pages |
4829-39
|
Published |
2012-9-15
|
DOI |
10.1158/0008-5472.CAN-12-0328
|
PII |
0008-5472.CAN-12-0328
|
PMID |
22826605
|
MeSH |
Adult
Aged
Aged, 80 and over
AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase
Animals
Antigens, Neoplasm / genetics*
Antigens, Neoplasm / metabolism
Apoptosis / physiology*
Biomarkers, Tumor / analysis
Blotting, Western
DNA Repair Enzymes / genetics*
DNA Repair Enzymes / metabolism
Dioxygenases / genetics*
Dioxygenases / metabolism
Female
Humans
Immunohistochemistry
Male
Mice
Mice, SCID
Middle Aged
Neovascularization, Pathologic / genetics*
Neovascularization, Pathologic / metabolism
Pancreatic Neoplasms / genetics*
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Tissue Array Analysis
Transfection
Xenograft Model Antitumor Assays
|
IF |
9.727
|
Resource |
Human and Animal Cells |
PANC-1(RCB2095)
MIA Paca2(RCB2094) |