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Experimental cell research v.361 no.2, 2017년, pp.308 - 315   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Targeting tumor cells based on Phosphodiesterase 3A expression

Nazir, Madiha (Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden ) ; Senkowski, Wojciech (Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden ) ; Nyberg, Frida (Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden ) ; Blom, Kristin (Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden ) ; Edqvist, Per-Henrik (Department of Immunology, Genetics and Pathology, Uppsala University, S-751 85 Uppsala, Sweden ) ; Jarvius, Malin (Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden ) ; Andersson, Claes (Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden ) ; Gustafsson, Mats G. (Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden ) ; Nygren, Peter (Department of Immunology, Genetics and Pathology, Uppsala University, S-751 85 Uppsala, Sweden ) ; Larsson, Rolf (Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden ) ; Fryknäs, Mårten (Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden ) ;
  • 초록  

    Abstract We and others have previously reported a correlation between high phosphodiesterase 3A ( PDE3A ) expression and selective sensitivity to phosphodiesterase (PDE) inhibitors. This indicates that PDE3 A could serve both as a drug target and a biomarker of sensitivity to PDE3 inhibition. In this report, we explored publicly available mRNA gene expression data to identify cell lines with different PDE3A expression. Cell lines with high PDE3A expression showed marked in vitro sensitivity to PDE inhibitors zardaverine and quazinone, when compared with those having low PDE3A expression. Immunofluorescence and immunohistochemical stainings were in agreement with PDE3A mRNA expression, providing suitable alternatives for biomarker analysis of clinical tissue specimens. Moreover, we here demonstrate that tumor cells from patients with ovarian carcinoma show great variability in PDE3A protein expression and that level of PDE3A expression is correlated with sensitivity to PDE inhibition. Finally, we demonstrate that PDE3A is highly expressed in subsets of patient tumor cell samples from different solid cancer diagnoses and expressed at exceptional levels in gastrointestinal stromal tumor (GIST) specimens. Importantly, vulnerability to PDE3 inhibitors has recently been associated with co-expression of PDE3A and Schlafen family member 12 ( SLFN12). We here demonstrate that high expression of PDE3A in clinical specimens, at least on the mRNA level, seems to be frequently associated with high SLFN12 expression. In conclusion, PDE3A seems to be both a promising biomarker and drug target for individualized drug treatment of various cancers. Highlights PDE3A mRNA overexpression correlates to PDE3A protein overexpression. High levels of PDE3A protein can be detected in clinical samples using IHC. Primary cells from subgroup of patients with high PDE3A respond to PDE3 inhibitors. PDE3A is overexpressed in subsets of patient derived samples from various tumors. Gastrointestinal stromal tumors show the highest expression of PDE3A .


  • 주제어

    Repositioning .   Cancer .   Therapy .   PDE3A .   Biomarker.  

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