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Reactivation of cAMP Pathway by PDE4D Inhibition Represents a Novel Druggable Axis for Overcoming Tamoxifen Resistance in ER-positive Breast Cancer.

Clin. Cancer Res.. 2018-04; 
MishraRasmi R,BelderNevin,AnsariSuhail A,KayhanMerve,BalHilal,RazaUmar,ErsanPelin G,TokatÜnal M,EyüpoğluErol,SaatciÖzge,JandaghiPouria,WiemannStefan,ÜnerAyşegül,CekicCaglar,RiazalhosseiniYasser,ŞahinÖz
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PCR and Cloning … Carlsbad, CA) according to manufacturer's instructions. PDE4D cDNA (NM_006203.4) present in pcDNA3.1+/C-(K) DYK mammalian expression vector (GenScript, USA) was used for overexpression experiments. Briefly, 50 ng … Get A Quote
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摘要

Tamoxifen remains an important hormonal therapy for ER-positive breast cancer; however, development of resistance is a major obstacle in clinics. Here, we aimed to identify novel mechanisms of tamoxifen resistance and provide actionable drug targets overcoming resistance. Whole-transcriptome sequencing, downstream pathway analysis, and drug repositioning approaches were used to identify novel modulators [here: phosphodiesterase 4D (PDE4D)] of tamoxifen resistance. Clinical data involving tamoxifen-treated patients with ER-positive breast cancer were used to assess the impact of PDE4D in tamoxifen resistance. Tamoxifen sensitization role of PDE4D was tested and Cytobiology, biochemistry, and functi... More

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