Regulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by DJ-1 in thyroid cancer cells.
DJ-1, a cancer-associated protein protects cells from multiple toxic stresses. The expression of DJ-1 and its influence on thyroid cancer cell death has not been investigated so far. We analyzed DJ-1 expression in human thyroid carcinoma cell lines and the effect of DJ-1 on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. DJ-1 was expressed in human thyroid carcinoma cell lines; small interfering RNA-mediated downregulation of its levels significantly sensitized thyroid carcinoma cells to TRAIL-induced apoptosis, whereas the forced exogenous expression of DJ-1 significantly suppressed cell death induced by TRAIL. We also report here that TRAIL-induced thyroid cancer cell apoptosis is mediated by oxidative stress and that DJ-1, a potent nutritional antioxidant, protects cancer cells from apoptosis at least in part by impeding the elevation of reactive oxygen species levels induced by TRAIL and impairing caspase-8 activation. Subsequently, we investigated DJ-1 expression in 52 normal and 74 primary thyroid carcinomas from patients of China Medical University. The protein was not detectable in the 52 specimens of normal thyroid, while 70 out of 74 analyzed carcinomas (33 out of 33 follicular, 17 out of 19 papillary, 12 out of 13 medullar, and 8 out of 9 anaplastic) were clearly positive for DJ-1 expression. Our data demonstrated that DJ-1 is specifically expressed in thyroid carcinomas and not in the normal thyroid tissue. In addition, the protein modulates the response to TRAIL-mediated apoptosis in human neoplastic thyroid cells, at least partially through its antioxidant property.
Zhang
Hai-Yan
HY
Department of Geriatrics, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
Wang
Hua-Qin
HQ
Liu
Hai-Mei
HM
Guan
Yifu
Y
Du
Zhen-Xian
ZX
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000502:physiology
D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; C505530:CASP8 protein, human; D053181:Caspase 8