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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-07-0195v1 15/2/535    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhang, H.-Y. Articles by Du, Z.-X. PubMed PubMed Citation Articles by Zhang, H.-Y. Articles by Du, Z.-X.

H Zhang, Geriatrics, China Medical University, Shenyang, China
H Wang, Biochemistry and Molecular Biology, China Medical University, Shenyang, 110001, China
H Liu, Shenyang, China
Y Guan, Shenyang, China
Z Du, Endocrinology & Metabolism, China Medical University, Shenyang, China

Correspondence: Hua-Qin Wang, Email: wanghq_doctor{at}hotmail.com

Abstract

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 TRAIL-induced apoptosis. DJ-1 was expressed in human thyroid carcinoma cell lines; siRNA-mediated downregulation of its levels significantly sensitized thyroid carcinoma cells to TRAIL-induced apoptosis; whereas 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 (ROS) levels induced by TRAIL and impairing caspase-8 activation. Subsequently, we investigated DJ-1 expression in 52 normal thyroid and 74 primary thyroid carcinomas from patients of China Medical University. The protein was not detectable in 52 specimens of normal thyroid, while 70 of 74 analyzed carcinomas (33 of 33 follicular, 17 of 19 papillary, 12 of 13 medullar and 8 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 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.