Evidence map›Paper›PMID 25837326›Full record

ArticleBreast cancer research : BCR2015

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

Betsy T Kren, Gretchen M Unger, Md J Abedin, Rachel I Vogel, Christine M Henzler, Khalil Ahmed, Janeen H Trembley

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.0field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 70 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Betsy T KrenResearch Service (151), Minneapolis VA Health Care System, One Veterans Drive, Minneapolis, MN 55417 USA ; Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street, SE, Minneapolis, MN USA ; Masonic Cancer Center, University of Minnesota, 717 Delaware Street SE Room 130, Minneapolis, MN 55414 USA.
Gretchen M UngerGeneSegues Inc, 3180 High Point, Chaska, MN 55318 USA.
Md J AbedinResearch Service (151), Minneapolis VA Health Care System, One Veterans Drive, Minneapolis, MN 55417 USA ; Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street, SE, Minneapolis, MN USA.
Rachel I VogelMasonic Cancer Center, University of Minnesota, 717 Delaware Street SE Room 130, Minneapolis, MN 55414 USA.
Christine M HenzlerDepartment of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street, SE, Minneapolis, MN USA ; Minnesota Supercomputing Institute, University of Minnesota, 117 Pleasant Street SE, Minneapolis, MN 55455 USA.
Khalil AhmedResearch Service (151), Minneapolis VA Health Care System, One Veterans Drive, Minneapolis, MN 55417 USA ; Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street, SE, Minneapolis, MN USA ; Masonic Cancer Center, University of Minnesota, 717 Delaware Street SE Room 130, Minneapolis, MN 55414 USA ; Department of Urology, University of Minnesota, 420 Delaware St. SE, Minneapolis, MN 55455 USA.
Janeen H TrembleyResearch Service (151), Minneapolis VA Health Care System, One Veterans Drive, Minneapolis, MN 55417 USA ; Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street, SE, Minneapolis, MN USA ; Masonic Cancer Center, University of Minnesota, 717 Delaware Street SE Room 130, Minneapolis, MN 55414 USA.
University of Minnesota · USMinneapolis VA Health Care System · USGenesegues (United States) · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
A Novel Therapeutic Approach for Primary and Metastatic Prostate CancerR01CA150182 · NCI · UNIVERSITY OF MINNESOTA · PI AHMED, KHALIL · 2011 to 2015
$1.4M
In Utero Correction of the OTC Defect in LiverR01DK067436 · NIDDK · UNIVERSITY OF MINNESOTA · PI KREN, BETSY T · 2007 to 2011
$1.4M
Tumor-targeted anti-CK2 RNAi for treatment of HCCR21CA158730 · NCI · UNIVERSITY OF MINNESOTA · PI KREN, BETSY T · 2012 to 2013
$284k
Antisense gene therapy with tumor-targeted nanocapsulesR43CA099366 · NCI · GENESEGUES, INC. · PI UNGER, GRETCHEN M · 2003 to 2003
$245k
Tumor-targeted delivery of siRNA via sub-50 nanometer capsulesR43CA119556 · NCI · GENESEGUES, INC. · PI UNGER, GRETCHEN M · 2006 to 2007
$199k
Modulation of Apoptosis in Prostate CancerI01BX001731 · VA · MINNEAPOLIS VA MEDICAL CENTER · PI AHMED, KHALIL · 2012 to 2015
–
BLRD VA I01 BX001731NCI NIH HHS CA119556NCI NIH HHS CA150182NCI NIH HHS CA158730NCI NIH HHS CA99366NCI NIH HHS HHS-N261-2008-00027/N42CM-2008-00027CNCI NIH HHS P30 CA077598NCI NIH HHS R01 CA150182NCI NIH HHS R21 CA158730NCI NIH HHS R43 CA099366NCI NIH HHS R43 CA119556NIDDK NIH HHS DK067436NIDDK NIH HHS R01 DK067436
6 · The paper itself

Abstract

introductionTargeted therapies for aggressive breast cancers like triple negative breast cancer (TNBC) are needed. The use of small interfering RNAs (siRNAs) to disable expression of survival genes provides a tool for killing these cancer cells. Cyclin dependent kinase 11 (CDK11) is a survival protein kinase that regulates RNA transcription, splicing and mitosis. Casein kinase 2 (CK2) is a survival protein kinase that suppresses cancer cell death. Eliminating the expression of these genes has potential therapeutic utility for breast cancer.

methodsExpression levels of CDK11 and CK2 mRNAs and associated proteins were examined in breast cancer cell lines and tissue arrays. RNA expression levels of CDC2L1, CDC2L2, CCNL1, CCNL2, CSNK2A1, CSNK2A2, and CSNK2B genes in breast cancer subtypes were analyzed. Effects following transfection of siRNAs against CDK11 and CK2 in cultured cells were examined by viability and clonal survival assays and by RNA and protein measures. Uptake of tenfibgen (TBG) nanocapsules by TNBC cells was analyzed by fluorescence-activated cell sorting. TBG nanocapsules delivered siRNAs targeting CDK11 or CK2 in mice carrying TNBC xenograft tumors. Transcript cleavage and response parameters were evaluated.

resultsWe found strong CDK11 and CK2 mRNA and protein expression in most human breast cancer cells. Immunohistochemical analysis of TNBC patient tissues showed 100% of tumors stained positive for CDK11 with high nuclear intensity compared to normal tissue. The Cancer Genome Atlas analysis comparing basal to other breast cancer subtypes and to normal breast revealed statistically significant differences. Down-regulation of CDK11 and/or CK2 in breast cancer cells caused significant loss of cell viability and clonal survival, reduced relevant mRNA and protein expression, and induced cell death changes. TBG nanocapsules were taken up by TNBC cells both in culture and in xenograft tumors. Treatment with TBG- siRNA to CDK11 or TBG- siRNA to CK2αα' nanocapsules induced appropriate cleavage of CDK11 and CK2α transcripts in TNBC tumors, and caused MDA-MB-231 tumor reduction, loss of proliferation, and decreased expression of targeted genes.

conclusionsCDK11 and CK2 expression are individually essential for breast cancer cell survival, including TNBC. These genes serve as promising new targets for therapeutic development in breast cancer.

Indexed as

RNA InterferenceAnimalsCasein Kinase IICell Line, TumorCell ProliferationCell SurvivalCyclin-Dependent KinasesDisease Models, AnimalFemaleGene ExpressionGene Expression Regulation, NeoplasticGene SilencingGenetic TherapyHumansImmunohistochemistryMiceCasein Kinase IICDK19 protein, humanCyclin-Dependent KinasesNanocapsulesRNA-Induced Silencing ComplexRNA, MessengerRNA, Small Interfering

Identifiers

PMID25837326
PMCPMC4344788
OpenAlexW2106261229

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.