title: N,N'-dinitrosopiperazine--mediated heat-shock protein 70-2 expression is involved in metastasis of nasopharyngeal carcinoma.
abstract: N,N'-Dinitrosopiperazine (DNP) is invovled in nasopharyngeal carcinoma (NPC) development and metastasis, and it shows organ specificity to the nasopharyngeal epithelium. Herein, we demonstrate that DNP induces heat-shock protein (HSP) 70-2 expression in NPC cells (6-10B) at a non-cytotoxic concentration. DNP induced HSP70-2 expression in a dose- and time- dependent manner, but showed no effect on other HSP70 family members. Furthermore, DNP also increased HSP70-2 RNA transcription through directly binding to the hypoxia-responsive elements (HRE) and heat shock elements (HSE) located in the HSP70-2 promoter. DNP-mediated HSP70-2 expression might act through enhancing the transcription of HSP70-2 RNA. Importantly, DNP induced motility and invasion of 6-10B cells dose- and time-dependently, and DNP-mediated NPC metastasis was confirmed in nude mice, which showed high HSP70-2 expression in the metastatic tumor tissue. However, the motility and invasion of NPC cells that were stably transfected using short interfering RNA against HSP70-2 could not effectively induce DNP. These results indicate that DNP induces HSP70-2 expression through increasing HSP70-2 transcription, increases the motility and invasion of cells, and promotes NPC tumor metastasis. Therefore, DNP mediated HSP70-2 expression may be an important factor of NPC-high metastasis.
authors.affiliation: Medical Research Center and Clinical Laboratory, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, People's Republic of China.
authors.forename: Zhengke
authors.initials: Z
authors.lastname: Peng
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Damao
authors.initials: D
authors.lastname: Huang
authors.forename: Chaojun
authors.initials: C
authors.lastname: Duan
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Tang
authors.forename: Wenhua
authors.initials: W
authors.lastname: Mei
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Faqing
authors.initials: F
authors.lastname: Tang
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009602:Nitrosamines / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D002273:Carcinogens; D018840:HSP70 Heat-Shock Proteins; D009602:Nitrosamines; C026156:N,N'-dinitrosopiperazine