Activating mutation (V617F) in the tyrosine kinase JAK2 is absent in locally-confined or castration-resistant prostate cancer

Lei Gu; Xian-Hua Zhu; Tapio Visakorpi; Kalle Alanen; Tuomas Mirtti; Tina Bocker Edmonston; Marja T. Nevalainen

doi:10.3233/ACP-2010-0534

$Background: Transcription factor Stat5a/b is highly critical for the viability of human prostate cancer cells in vitro and for prostate tumor growth in vivo. Stat5 is constitutively active in clinical prostate cancers but not in the normal human prostate epithelium. Moreover, Stat5a/b activation in prostate cancer is associated with high histological grade of prostate cancer. However, the molecular mechanisms underlying constitutive activation of Stat5a/b in prostate cancer are unclear. The receptor-associated tyrosine kinase Jak2 is a known key activator of Stat5a/b in prostate cancer cells in response to ligand stimulation. Recently, a single gain-of-function point mutation of JAK2 was described in myeloproliferative diseases leading to constitutive Jak2 kinase activity, subsequent Stat5a/b activation and involvement of V617F Jak2 in the pathogenesis of myeloproliferative disorders. Materials and methods: We determined whether JAK2 undergoes the V617F activating mutation during clinical progression of human prostate cancer using a highly sensitive assay (amplification refractory mutation system) and a unique material of fresh specimens from organ-confined or castration-resistant prostate cancers. Results: The JAK2 V617F mutation was not found in any of the normal or malignant prostate samples analyzed in this study. Conclusions: Future work should focus on determining the molecular mechanisms other than V617F mutation of Jak2 resulting in continuous Stat5 activation in clinical prostate cancers.$

Activating mutation (V617F) in the tyrosine kinase JAK2 is absent in locally-confined or castration-resistant prostate cancer

Gu, Lei; Zhu, Xian-Hua; Visakorpi, Tapio; Alanen, Kalle; Mirtti, Tuomas; Edmonston, Tina Bocker; Nevalainen, Marja T.

Follow Analytical Cellular Pathology , Volume 33 (2) IOS Press – Jan 1, 2010