title: PACAP inhibits tumor growth and interferes with clusterin in cervical carcinomas.
abstract: Secretory clusterin (sCLU), an anti-apoptotic protein, is overexpressed in many tumors and enhances tumorigenesis and chemo-resistance. However, the regulation mechanism controlling the sCLU maturation process or activity remains undetermined. In this study, we found PACAP as a negative regulator of CLU. Overexpression of the PACAP gene in cervical cancer cell lines lacking PACAP expression significantly inhibited cell growth and induced apoptosis. We further demonstrated that interaction of PACAP with CLU significantly downregulated CLU expression and secretion, inhibited the Akt-Raf-ERK pathway, and suppressed the growth of human tumor xenografts in nude mice. This novel inhibitory function of PACAP may be applicable for developing novel molecular therapies for tumors with increased sCLU expression.
authors.affiliation: Department of Life Science, YongIn University, 470 Samga-dong Chuingu, Yonginsi, South Korea; Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, South Korea.
authors.forename: Ji-Hae
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Life Science, YongIn University, 470 Samga-dong Chuingu, Yonginsi, South Korea; Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, South Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, South Korea.
authors.forename: Seung Bae
authors.initials: SB
authors.lastname: Rho
authors.affiliation: Division of Life Science, Korea Basic Science Institute, Daejeon 305-806, South Korea.
authors.forename: Jong-Soon
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Division of Life Science, Korea Basic Science Institute, Daejeon 305-806, South Korea.
authors.forename: Dong-Gi
authors.initials: DG
authors.lastname: Lee
authors.affiliation: Genomictree, Inc., 829 Tamnip-dong, Yuseong, Daejeon, South Korea.
authors.forename: Sungwhan
authors.initials: S
authors.lastname: An
authors.affiliation: Genomictree, Inc., 829 Tamnip-dong, Yuseong, Daejeon, South Korea.
authors.forename: Taejeong
authors.initials: T
authors.lastname: Oh
authors.affiliation: Department of Life Science, YongIn University, 470 Samga-dong Chuingu, Yonginsi, South Korea.
authors.forename: Don-Chan
authors.initials: DC
authors.lastname: Choi
authors.affiliation: Department of Life Science, YongIn University, 470 Samga-dong Chuingu, Yonginsi, South Korea. Electronic address: shlee@yongin.ac.kr.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D051152:Clusterin / Q000737:chemistry / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D048490:raf Kinases / Q000378:metabolism
chemical_list: D051152:Clusterin; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051057:Proto-Oncogene Proteins c-akt; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Akt/Raf/ERK pathway; Apoptosis; Cervical cancer; Clusterin; Pituitary adenylate cyclase-activating polypeptide