Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel up-regulated secretory protein in pancreatic ductal adenocarcinoma.
The identification of novel tumor-specific proteins or antigens is of great importance for diagnostic and therapeutic applications in pancreatic cancer. Using oligonucleotide microarrays, we identified a broad spectrum of differentially expressed pancreatic cancer-related genes. Of these, we selected an overexpressed expressed sequence taq and cloned a 721-bp full-length cDNA with an open reading frame of 196 amino acids. This novel gene was localized on the Homo sapiens 16p13.3 chromosomal locus, and its nucleotide sequence matched the Homo sapiens similar to common salivary protein 1 (LOC124220). We named the gene pancreatic adenocarcinoma up-regulated factor. The pancreatic adenocarcinoma up-regulated factor was secreted into the culture medium of pancreatic adenocarcinoma up-regulated factor-overexpressing Chinese hamster ovary cells, had an apparent molecular mass of approximately 25 kDa, and was N-glycosylated. The induction of pancreatic adenocarcinoma up-regulated factor in Chinese hamster ovary cells increased cell proliferation, migration, and invasion ability in vitro. Subcutaneous injection of mice with Chinese hamster ovary/pancreatic adenocarcinoma up-regulated factor cells resulted in 3.8-fold greater tumor sizes compared to Chinese hamster ovary/mock cells. Reverse transcription-polymerase chain reaction and western blotting with antirecombinant human pancreatic adenocarcinoma up-regulated factor antibodies confirmed that pancreatic adenocarcinoma up-regulated factor was highly expressed in six of eight pancreatic cancer cell lines. Immunohistochemical staining of human pancreatic cancer tissues also showed pancreatic adenocarcinoma up-regulated factor overexpression in the cytoplasm of cancer cells. Transfection with pancreatic adenocarcinoma up-regulated factor-specific small-interfering RNA reduced cancer cell migration and invasion in vitro. Treatment with antirecombinant human pancreatic adenocarcinoma up-regulated factor in vitro and in vivo reduced proliferation, migration, invasion, and tumorigenic ability. Collectively, our results suggest that pancreatic adenocarcinoma up-regulated factor is a novel secretory protein involved in pancreatic cancer progression and might be a potential target for the treatment of pancreatic cancer.
Kim
Sun A
SA
Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
Lee
Yangsoon
Y
Jung
Dawoon E
DE
Park
Kyung Hwa
KH
Park
Jeong Youp
JY
Gang
Jingu
J
Jeon
Sun Bok
SB
Park
Eui Chul
EC
Kim
Young-Gun
YG
Lee
Bogman
B
Liu
Qing
Q
Zeng
Wen
W
Yeramilli
Subramanyam
S
Lee
Soojin
S
Koh
Sang Seok
SS
Song
Si Young
SY
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D000906:Antibodies; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C517340:ZG16B protein, human