title: Depletion of Jab1 inhibits proliferation of pancreatic cancer cell lines.
abstract: Jab1 overexpression is observed in many human cancers, but its physiological significance remains to be investigated. We reduced the level of Jab1 expression in pancreatic cancer cell lines, MIA PaCa-2 and PANC-1 by the RNA interference and found that Jab1-knockdown resulted in impaired cell proliferation and enhanced apoptosis regardless of the genotype of the tumor suppressor p53. This growth inhibition was rescued by the introduction of siRNA-resistant mouse Jab1 cDNA. Jab1-knocked-down cells expressed a higher level of c-myc, and additional depletion of c-myc rescued cells from Jab1-knockdown-mediated growth suppression. Thus, Jab1 overexpression contributes to pancreatic cancer cell proliferation and survival. Jab1 could be a novel target in cancer therapy.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Fukumoto
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Tomoda
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoneda-Kato
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Jun-ya
authors.initials: JY
authors.lastname: Kato
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D000075686:COP9 Signalosome Complex; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000235:genetics; D016193:G1 Phase; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; C501490:Cops5 protein, mouse; D000075686:COP9 Signalosome Complex