RRC ID 69445
著者 Yamato I, Sho M, Shimada K, Hotta K, Ueda Y, Yasuda S, Shigi N, Konishi N, Tsujikawa K, Nakajima Y.
タイトル PCA-1/ALKBH3 contributes to pancreatic cancer by supporting apoptotic resistance and angiogenesis.
ジャーナル 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.
巻・号 72(18)
ページ 4829-39
公開日 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
リソース情報
ヒト・動物細胞 PANC-1(RCB2095) MIA Paca2(RCB2094)