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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...

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Autores principales: Gu, Lei, Zhu, Xian-Hua, Visakorpi, Tapio, Alanen, Kalle, Mirtti, Tuomas, Edmonston, Tina Bocker, Nevalainen, Marja T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605774/
https://www.ncbi.nlm.nih.gov/pubmed/20966544
http://dx.doi.org/10.3233/ACP-CLO-2010-0534
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author Gu, Lei
Zhu, Xian-Hua
Visakorpi, Tapio
Alanen, Kalle
Mirtti, Tuomas
Edmonston, Tina Bocker
Nevalainen, Marja T.
author_facet Gu, Lei
Zhu, Xian-Hua
Visakorpi, Tapio
Alanen, Kalle
Mirtti, Tuomas
Edmonston, Tina Bocker
Nevalainen, Marja T.
author_sort Gu, Lei
collection PubMed
description 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.
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spelling pubmed-46057742015-12-13 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. Anal Cell Pathol (Amst) Other 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. IOS Press 2010 2010-08-10 /pmc/articles/PMC4605774/ /pubmed/20966544 http://dx.doi.org/10.3233/ACP-CLO-2010-0534 Text en Copyright © 2010 Hindawi Publishing Corporation and the authors.
spellingShingle Other
Gu, Lei
Zhu, Xian-Hua
Visakorpi, Tapio
Alanen, Kalle
Mirtti, Tuomas
Edmonston, Tina Bocker
Nevalainen, Marja T.
Activating Mutation (V617F) in the Tyrosine Kinase JAK2 is Absent in Locally-Confined or Castration-Resistant Prostate Cancer
title Activating Mutation (V617F) in the Tyrosine Kinase JAK2 is Absent in Locally-Confined or Castration-Resistant Prostate Cancer
title_full Activating Mutation (V617F) in the Tyrosine Kinase JAK2 is Absent in Locally-Confined or Castration-Resistant Prostate Cancer
title_fullStr Activating Mutation (V617F) in the Tyrosine Kinase JAK2 is Absent in Locally-Confined or Castration-Resistant Prostate Cancer
title_full_unstemmed Activating Mutation (V617F) in the Tyrosine Kinase JAK2 is Absent in Locally-Confined or Castration-Resistant Prostate Cancer
title_short Activating Mutation (V617F) in the Tyrosine Kinase JAK2 is Absent in Locally-Confined or Castration-Resistant Prostate Cancer
title_sort activating mutation (v617f) in the tyrosine kinase jak2 is absent in locally-confined or castration-resistant prostate cancer
topic Other
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605774/
https://www.ncbi.nlm.nih.gov/pubmed/20966544
http://dx.doi.org/10.3233/ACP-CLO-2010-0534
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