Targeting janus kinase 2 in Her2/neu-expressing mammary cancer

Implications for cancer prevention and therapy

Kazuhito Sakamoto, Wan Chi Lin, Aleata A. Triplett, Kay-Uwe Wagner

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The Janus kinase 2 (Jak2) is essential for normal mammary gland development, but this tyrosine kinase and its main effector, signal transducer and activator of transcription 5, are also active in a significant subset of human breast cancers. We have recently reported that Jak2 controls the expression and nuclear accumulation of cyclin D1. Because this particular Dtype cyclin has been suggested to be a key mediator for ErbB2-associated mammary tumorigenesis, we deleted Jak2 from ErbB2-expressing mammary epithelial cells prior to tumor onset and in neoplastic cells to address whether this tyrosine kinase plays a role in the initiation as well as progression of mammary cancer. Similar to cyclin D1-deficient mice, the functional ablation of Jak2 protects against the onset of mammary tumorigenesis. In contrast, the deletion of Jak2 from neoplastic cells or the acute, ligand-inducible downregulation of this tyrosine kinase in an orthotopic transplant model did not affect the growth and survival of cancer cells. The constitutive activation of ErbB2 signaling, which is an initial event in the formation of mammary cancer, was able to override the functional role of Jak2 in regulating the expression of Akt1 and cyclin D1. This might be a compensatory mechanism that explains why Jak2 is a relevant target for preventing the initiation but not the progression of ErbB2-associated mammary cancer.

Original languageEnglish (US)
Pages (from-to)6642-6650
Number of pages9
JournalCancer Research
Volume69
Issue number16
DOIs
StatePublished - Aug 15 2009

Fingerprint

Janus Kinase 2
Breast Neoplasms
Cyclin D1
Neoplasms
Protein-Tyrosine Kinases
Breast
Therapeutics
Carcinogenesis
STAT5 Transcription Factor
Cyclins
Human Mammary Glands
Cell Survival
Down-Regulation
Epithelial Cells
Ligands
Transplants
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Targeting janus kinase 2 in Her2/neu-expressing mammary cancer : Implications for cancer prevention and therapy. / Sakamoto, Kazuhito; Lin, Wan Chi; Triplett, Aleata A.; Wagner, Kay-Uwe.

In: Cancer Research, Vol. 69, No. 16, 15.08.2009, p. 6642-6650.

Research output: Contribution to journalArticle

Sakamoto, Kazuhito ; Lin, Wan Chi ; Triplett, Aleata A. ; Wagner, Kay-Uwe. / Targeting janus kinase 2 in Her2/neu-expressing mammary cancer : Implications for cancer prevention and therapy. In: Cancer Research. 2009 ; Vol. 69, No. 16. pp. 6642-6650.
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