title: Oxidative stress induces ADAM9 protein expression in human prostate cancer cells.
abstract: The ADAM (a disintegrin and metalloprotease) family is a group of transmembrane proteins containing cell adhesive and proteolytic functional domains. Microarray analysis detected elevated ADAM9 during the transition of human LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent and metastatic state. Using a prostate tissue array (N = 200), the levels of ADAM9 protein expression were also elevated in malignant as compared with benign prostate tissues. ADAM9 protein expression was found in 43% of benign glands with light staining and 87% of malignant glands with increasing intensity of staining. We found that ADAM9 mRNA and protein expressions were elevated on exposure of human prostate cancer cells to stress conditions such as cell crowding, hypoxia, and hydrogen peroxide. We uncovered an ADAM9-like protein, which is predominantly induced together with the ADAM9 protein by a brief exposure of prostate cancer cells to hydrogen peroxide. Induction of ADAM9 protein in LNCaP or C4-2 cells can be completely abrogated by the administration of an antioxidant, ebselen, or genetic transfer of a hydrogen peroxide degradative enzyme, catalase, suggesting that reactive oxygen species (ROS) are a common mediator. The induction of ADAM9 by stress can be inhibited by both actinomycin D and cycloheximide through increased gene transcription and protein synthesis. In conclusion, intracellular ROS and/or hydrogen peroxide, generated by cell stress, regulate ADAM9 expression. ADAM9 could be responsible for supporting prostate cancer cell survival and progression. By decreasing ADAM9 expression, we observed apoptotic cell death in prostate cancer cells.
authors.affiliation: Molecular Urology and Therapeutics Program, Department of Urology, Emory University School of Medicine, Atlanta, GA 30322, USA. ssung2@emory.edu
authors.forename: Shian-Ying
authors.initials: SY
authors.lastname: Sung
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kubo
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shigemura
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Arnold
authors.forename: Sanjay
authors.initials: S
authors.lastname: Logani
authors.forename: Ruoxiang
authors.initials: R
authors.lastname: Wang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Spiro
authors.initials: S
authors.lastname: Mousses
authors.forename: Mahul
authors.initials: M
authors.lastname: Amin
authors.forename: Cynthia
authors.initials: C
authors.lastname: Anderson
authors.forename: Peter
authors.initials: P
authors.lastname: Johnstone
authors.forename: John A
authors.initials: JA
authors.lastname: Petros
authors.forename: Fray F
authors.initials: FF
authors.lastname: Marshall
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D000728:Androgens; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D001393:Azoles / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016566:Organoselenium Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000728:Androgens; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D003609:Dactinomycin; C042986:ebselen; D003513:Cycloheximide; D006861:Hydrogen Peroxide; D002374:Catalase; D051722:ADAM Proteins; C098339:ADAM9 protein, human