title: DUSP28 links regulation of Mucin 5B and Mucin 16 to migration and survival of AsPC-1 human pancreatic cancer cells.
abstract: The prognosis of pancreatic cancer has not improved despite considerable and continuous effort. Dual-specificity phosphatase 28 (DUSP28) is highly expressed in human pancreatic cancers and exerts critical effects. However, knowledge of its function in pancreatic cancers is extremely limited. Here, we demonstrate the peculiar role of DUSP28 in pancreatic cancers. Analysis using the Gene Expression Omnibus public microarray database indicated higher DUSP28, MUC1, MUC4, MUC5B, MUC16 and MUC20 messenger RNA (mRNA) levels in pancreatic cancers compared with normal pancreas tissues. DUSP28 expression in human pancreatic cancer correlated positively with those of MUC1, MUC4, MUC5B, MUC16 and MUC20. In contrast, there were no significant correlations between DUSP28 and mucins in normal pancreas tissues. Decreased DUSP28 expression resulted in down-regulation of MUC5B and MUC16 at both the mRNA and protein levels; furthermore, transfection with small interfering RNA (siRNA) for MUC5B and MUC16 inhibited the migration and survival of AsPC-1 cells. In addition, transfection of siRNA for MUC5B and MUC16 resulted in a significant decrease in phosphorylation of FAK and ERK1/2 compared with transfection with scrambled-siRNA. These results collectively indicate unique links between DUSP28 and MUC5B/MUC16 and their roles in pancreatic cancer; moreover, they strongly support a rationale for targeting DUSP28 to inhibit development of malignant pancreatic cancer.
authors.affiliation: Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University, Jeju-do, 63243, Korea. sdjd1108@kaist.ac.kr.
authors.forename: Jungwhoi
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Korea.
authors.forename: Jungsul
authors.initials: J
authors.lastname: Lee
authors.affiliation: Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University, Jeju-do, 63243, Korea.
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Yun
authors.affiliation: Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, South Korea.
authors.forename: Dae Gwin
authors.initials: DG
authors.lastname: Jeong
authors.affiliation: Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University, Jeju-do, 63243, Korea. kimjh@jejunu.ac.kr.|Subtropical Horticulture Research Institute, Jeju National University, Jeju, 63243, Korea. kimjh@jejunu.ac.kr.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D018394:CA-125 Antigen / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D054637:Dual-Specificity Phosphatases / Q000235:genetics* / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D055257:Mucin-5B / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018394:CA-125 Antigen; D055257:Mucin-5B; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054637:Dual-Specificity Phosphatases
keywords: AsPC-1 cells; DUSP28; MUC16; MUC5B; Migration; Survival