title: TTP mediates cisplatin-induced apoptosis of head and neck cancer cells by down-regulating the expression of Bcl-2.
abstract: The chemotherapeutic agent cisplatin is widely used for treatment of head and neck squamous cell carcinoma (HNSCC). B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic protein that is overexpressed in cancer cells and confers resistance to cisplatin. Thus, inhibition of Bcl-2 expression may enhance the cisplatin sensitivity of cancer cells. In this study, we report that the AU-rich element (ARE) binding protein tristetraprolin (TTP) inhibits the expression of Bcl-2 and enhances cisplatin sensitivity of HNSCC cells. Cisplatin-sensitive HNSCC cells express high levels of TTP and low levels of Bcl-2, while cisplatin-resistant HNSCC cells have low levels of TTP and high levels of Bcl-2. Inhibition of TTP expression using siRNA increases levels of Bcl-2 and decreases cisplatin sensitivity in HNSCC cells. On the contrary, overexpression of TTP decreases Bcl-2 expression and increases sensitivity to cisplatin. Together, the results of the present study suggest that TTP expression enhances cisplatin sensitivity in HNSCC cells by reducing levels of Bcl-2.
authors.forename: Su Bien
authors.initials: SB
authors.lastname: Park
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Won Wook
authors.initials: WW
authors.lastname: Jeong
authors.forename: Yo Hwan
authors.initials: YH
authors.lastname: Kim
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Cha
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Joe
authors.forename: Hun Taeg
authors.initials: HT
authors.lastname: Chung
authors.forename: Wha Ja
authors.initials: WJ
authors.lastname: Cho
authors.forename: Jeong Wan
authors.initials: JW
authors.lastname: Do
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Byung Kyun
authors.initials: BK
authors.lastname: Ko
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D002945:Cisplatin
keywords: Bcl-2,; Cisplatin sensitivity,; Head and neck squamous cell carcinoma; TTP,