Article

Effects of the Cyclin-Dependent Kinase 10 (CDK10) on the Tamoxifen Sensitivity of Keloid Samples

Department of Plastic and Aesthetic, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Molecules (Impact Factor: 2.1). 12/2012; 17(2):1307-18. DOI: 10.3390/molecules17021307
Source: PubMed

ABSTRACT Cyclin-dependent kinase 10 (CDK10) is a cell cycle regulating protein kinase, which has just been discriminated in recent years. In this paper, mRNA and protein expression of CDK10 were first investigated by a comparative study between 23 human keloid tissue samples and their adjacent normal skin. To further address its potential as a therapeutic target in the treatment of keloid, a plasmid expressing the CDK10 gene was transfected into keloid fibroblast. The effects on tamoxifen-induced apoptosis were then investigated using Western blot assay and flow cytometry. Results showed that there is a generally down-regulated expression of CDK10 in keloid compared to normal skin samples. Transfection with the recombinant CDK10 plasmid significantly decreased the viability of cells and increased the apoptosis rates. Tamoxifen sensitivity in keloid fibroblasts was observed after treatment with the recombinant CDK10 plasmid. The results suggested that CDK10 may play an important role in enhancement of tamoxifen efficiency, and its expression may have a synergistic effect on keloid treatments.

0 Followers
 · 
96 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The insect steroid hormone 20E-hydroxyecdysone (20E) regulates gene transcription via a genomic pathway by forming a transcription complex that binds to DNA with the help of the chaperone proteins Hsc70 and Hsp90. However, the non-genomic mechanisms by which 20E regulates gene expression remain unclear. In this study, we found that 20E regulated the phosphorylation of serine/threonine protein kinase cyclin-dependent kinase 10 (CDK10) through a non-genomic pathway to mediate gene transcription in the lepidopteran Helicoverpa armigera. The downregulation of CDK10 by RNA interference in larvae and the epidermal cell line delayed development and suppressed 20E-induced gene transcription. CDK10 was localized to the nucleus via its KKRR motif, and this nuclear localization and the ATPase motif were necessary for the efficient expression of 20E-inducible gene. The rapid phosphorylation of CDK10 was induced by 20E, whereas it was repressed by the inhibitors of G-protein-coupled receptors, phospholipase C, and Ca(2+) channels. Phosphorylated CDK10 exhibited increased interactions with heat shock proteins (Hsps) Hsc70 and Hsp90 and then promoted the interactions between Hsps and ecdysone receptor EcRB1 and the binding of Hsps-EcRB1 complex to the 20E response element for the regulation of gene transcription. CDK10 depletion suppressed the formation of the Hsps-EcRB1 complex at HR3 promoter. These results suggest that 20E induces CDK10 phosphorylation via a non-genomic pathway to regulate gene transcription in the nucleus.
    Endocrinology 02/2014; 155(5):en20132020. DOI:10.1210/en.2013-2020 · 4.64 Impact Factor

Preview

Download
1 Download
Available from