Oxidative stress induces ADAM9 protein expression in human prostate cancer cells.
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.
Sung
Shian-Ying
SY
Molecular Urology and Therapeutics Program, Department of Urology, Emory University School of Medicine, Atlanta, GA 30322, USA. ssung2@emory.edu
Kubo
Hiroyuki
H
Shigemura
Katsumi
K
Arnold
Rebecca S
RS
Logani
Sanjay
S
Wang
Ruoxiang
R
Konaka
Hiroyuki
H
Nakagawa
Masayuki
M
Mousses
Spiro
S
Amin
Mahul
M
Anderson
Cynthia
C
Johnstone
Peter
P
Petros
John A
JA
Marshall
Fray F
FF
Zhau
Haiyen E
HE
Chung
Leland W K
LW
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
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