Identification of C2orf18, termed ANT2BP (ANT2-binding protein), as one of the key molecules involved in pancreatic carcinogenesis.
Pancreatic ductal adenocarcinoma (PDAC) shows one of the worst mortality rates among the common malignancies, and the great majority of PDAC patients are diagnosed at an advanced stage where no effective therapy is presently available. Hence, identification of novel molecular targets and development of molecular therapy for PDAC are urgently required. Through our genome-wide gene expression profiles of microdissected PDAC cells, we here identified a novel gene C2orf18 as a molecular target for PDAC treatment. Transcriptional and immunohistochemical analysis validated its overexpression in PDAC cells and limited expression in normal adult organs. Knockdown of C2orf18 by small-interfering RNA in PDAC cell lines resulted in induction of apoptosis and suppression of cancer cell growth, suggesting its essential role in maintaining viability of PDAC cells. We showed that C2orf18 was localized in the mitochondria and it could interact with adenine nucleotide translocase 2 (ANT2), which is involved in maintenance of the mitochondrial membrane potential and energy homeostasis, and was indicated some roles in apoptosis. These findings implicated that C2orf18, termed ANT2-binding protein (ANT2BP), might serve as a candidate molecular target for pancreatic cancer therapy.
Kashiwaya
Kotoe
K
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Hosokawa
Masayo
M
Eguchi
Hidetoshi
H
Ohigashi
Hiroaki
H
Ishikawa
Osamu
O
Shinomura
Yasuhisa
Y
Nakamura
Yusuke
Y
Nakagawa
Hidewaki
H
D033742:Adenine Nucleotide Translocator 2 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D015152:Blotting, Northern; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D045744:Cell Line, Tumor; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008928:Mitochondria / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D033742:Adenine Nucleotide Translocator 2; D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins