ArticleThe Journal of biological chemistry2005
Down-regulation of ATM protein sensitizes human prostate cancer cells to radiation-induced apoptosis.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 57 citations in OpenAlex.
- Molecular Mechanism and Research Progress of Sphingolipid Metabolism in Regulating Radiation-induced Apoptosis Using Pan-cancer Analysis.Current cancer drug targets · 2026Review
- Anti-cancer potential of zerumbone in cancer and glioma: current trends and future perspectives.Medical oncology (Northwood, London, England) · 2024Review
- Acid Sphingomyelinase-Ceramide Induced Vascular Injury Determines Colorectal Cancer Stem Cell Fate.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2022Article
- Identification of an integrated stress and growth response signaling switch that directs vertebrate intestinal regeneration.BMC genomics · 2022Article
- Autophagic Organelles in DNA Damage Response.Frontiers in cell and developmental biology · 2021Review
- Comparative lipidomics of 5-Fluorouracil-sensitive and -resistant colorectal cancer cells reveals altered sphingomyelin and ceramide controlled by acid sphingomyelinase (SMPD1).Scientific reports · 2020Article
- miRNA-106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation.Molecular oncology · 2018Article
- Evolving concepts in cancer therapy through targeting sphingolipid metabolism.Biochimica et biophysica acta · 2014Review
- The effect of radiation on the immune response to cancers.International journal of molecular sciences · 2014Review
- Honokiol as a Radiosensitizing Agent for Colorectal cancers.Current colorectal cancer reports · 2013Article
- Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse.The Journal of clinical investigation · 2013Article
- Ceramide-orchestrated signalling in cancer cells.Nature reviews. Cancer · 2013Review
- Upon the tightrope in prostate cancer: two acrobats on the same tightrope to cross the finishline.Molecular and cellular biochemistry · 2012Review
- Ceramide synthases at the centre of sphingolipid metabolism and biology.The Biochemical journal · 2012Review
- Article
- Down-regulation of EBV-LMP1 radio-sensitizes nasal pharyngeal carcinoma cells via NF-κB regulated ATM expression.PloS one · 2011Article
- Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells.Cellular signalling · 2010Article
- Ceramide-rich platforms in transmembrane signaling.FEBS letters · 2010Review
- Regulation of ceramide synthase-mediated crypt epithelium apoptosis by DNA damage repair enzymes.Cancer research · 2010Article
- ROCK mediates phorbol ester-induced apoptosis in prostate cancer cells via p21Cip1 up-regulation and JNK.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Treatment with the protein kinase C activator 12-O-tetradecanoylphorbol 12-acetate (TPA) enables radiation-resistant LNCaP human prostate cancer cells to undergo radiation-induced apoptosis, mediated via activation of the enzyme ceramide synthase (CS) and de novo synthesis of the sphingolipid ceramide (Garzotto, M., Haimovitz-Friedman, A., Liao, W. C., White-Jones, M., Huryk, R., Heston, D. W. W., Cardon-Cardo, C., Kolesnick, R., and Fuks, Z. (1999) Cancer Res. 59, 5194-5201). Here, we show that TPA functions to decrease the cellular level of the ATM (ataxia telangiectasia mutated) protein, known to repress CS activation (Liao, W.-C., Haimovitz-Friedman, A., Persaud, R., McLoughlin, M., Ehleiter, D., Zhang, N., Gatei, M., Lavin, M., Kolesnick, R., and Fuks, Z. (1999) J. Biol. Chem. 274, 17908-17917). Gel shift analysis in LNCaP and CWR22-Rv1 cells demonstrated a significant reduction in DNA binding of the Sp1 transcription factor to the ATM promoter, and quantitative reverse transcription-PCR showed a 50% reduction of ATM mRNA between 8 and 16 h of TPA treatment, indicating that TPA inhibits ATM transcription. Furthermore, treatment of LNCaP, CWR22-Rv1, PC-3, and DU-145 human prostate cells with antisense-ATM oligonucleotides, which markedly reduced cellular ATM levels, significantly enhanced radiation-induced CS activation and apoptosis, leading to apoptosis at doses as a low as 1 gray. These data suggest that the CS pathway initiates a generic mode of radiation-induced apoptosis in human prostate cancer cells, regulated by a suppressive function of ATM, and that ATM might represent a potential target for pharmacologic inactivation with potential clinical applications in human prostate cancer.
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