Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets for triple negative breast cancer therapy

• DOI: 10.1186/s13058-015-0524-0
• Publication Date: 2015-02-10T14:42:33Z
• Authors: Betsy T Kren; Gretchen M Unger; Md J Abedin; Rachel I Vogel; Christine M Henzler; Khalil Ahmed; Janeen H Trembley
• Keywords: Surgical oncology; Cyclin-dependent kinase 4; Triple-negative breast cancer

Targeted therapies for aggressive breast cancers like triple negative cancer (TNBC) are needed. The use of small interfering RNAs (siRNAs) to disable expression survival genes provides a tool killing these cells. Cyclin dependent kinase 11 (CDK11) is protein that regulates RNA transcription, splicing and mitosis. Casein 2 (CK2) suppresses cell death. Eliminating the has potential therapeutic utility cancer.Expression levels CDK11 CK2 mRNAs associated proteins were examined in lines tissue arrays. CDC2L1, CDC2L2, CCNL1, CCNL2, CSNK2A1, CSNK2A2, CSNK2B subtypes analyzed. Effects following transfection siRNAs against cultured cells by viability clonal assays measures. Uptake tenfibgen (TBG) nanocapsules TNBC was analyzed fluorescence-activated sorting. TBG delivered targeting or mice carrying xenograft tumors. Transcript cleavage response parameters evaluated.We found strong mRNA most human Immunohistochemical analysis patient tissues showed 100% tumors stained positive with high nuclear intensity compared normal tissue. Cancer Genome Atlas comparing basal other revealed statistically significant differences. Down-regulation and/or caused loss survival, reduced relevant expression, induced death changes. taken up both culture Treatment TBG- siRNA CK2αα' appropriate CK2α transcripts tumors, MDA-MB-231 tumor reduction, proliferation, decreased targeted genes.CDK11 individually essential including TNBC. These serve as promising new targets development cancer.