title: Functional analysis of the TMPRSS2:ERG fusion gene in cisplatin‑induced cell death.
abstract: The TMPRSS2:E‑twenty‑six (ETS) gene fusion occurs frequently in a high proportion of patients with prostate cancer (PCa) in Western countries, and the aberrant expression of TMPRSS2: v‑ETS avian erythroblastosis virus E26 oncogene homolog (ERG), the most common form of the corresponding protein, can regulate cell migration and contribute to tumor invasion and metastasis. However, its association with other cellular events, and in particular, cell death, remain unknown. To examine the function of such fusion genes, an expression plasmid containing the TMPRSS2:ERG (T1/E5) sequence (ΔERG) from a patient sample was constructed and transiently transfected into DU145 cells, which do not express the fusion gene. It was found that the overexpression of ΔERG significantly inhibited the ability of cisplatin to induce apoptosis in DU145 cells. By contrast, VCaP cells, which do contain TMPRSS2:ERG, were sensitized to cisplatin‑induced apoptosis through siRNA inhibition of the fusion gene. To elucidate the underlying mechanism, a stable cell line expressing the ΔERG gene was constructed. Expression of ΔERG did not affect cell migration, but did protect cells from DNA damage and apoptosis induced by cisplatin. Furthermore, knockdown of ΔERG by short interfering RNA resulted in cells regaining their sensitivity to cisplatin. Finally, the gene coding for activating transcription factor 5, which is important for cell survival, may be upregulated by ΔERG. Taken together, these data point to a new function of the TMPRSS2:ERG fusion gene in regulating the apoptotic pathway.
authors.affiliation: Clinical Laboratory, Jinhua Hospital of Zhejiang University, Jinhua, Zhejiang 321000, P.R. China.
authors.forename: Junqi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Chi
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Zhanghui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Lishui People's Hospital, Lishui, Zhejiang 323000, P.R. China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Suping
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jindan
authors.initials: J
authors.lastname: Luo
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Ge-Ming
authors.initials: GM
authors.lastname: Chen
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D051696:Activating Transcription Factors / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D002945:Cisplatin / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: C507532:ATF5 protein, human; D051696:Activating Transcription Factors; D015514:Oncogene Proteins, Fusion; D034741:RNA, Small Interfering; C515553:TMPRSS2-ERG fusion protein, human; D002945:Cisplatin