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


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.
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Lei
L
Gu
Xian-Hua
XH
Zhu
Tapio
T
Visakorpi
Kalle
K
Alanen
Tuomas
T
Mirtti
Tina Bocker
TB
Edmonston
Marja T
MT
Nevalainen
D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D009154:Mutation; D009919:Orchiectomy; D016133:Polymerase Chain Reaction; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D050799:STAT5 Transcription Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2