Depletion of Jab1 inhibits proliferation of pancreatic cancer cell lines.
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.
Fukumoto
Akihisa
A
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
Tomoda
Kiichiro
K
Yoneda-Kato
Noriko
N
Nakajima
Yoshiyuki
Y
Kato
Jun-ya
JY
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
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