Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 38, Pages 16369-16374Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0907044106
Keywords
IL-6; PSA; recurrence
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Funding
- Ministry of Education, Culture, Science, and Technology
- Japan Society for the Promotion of Science
- Strategic Research Promotion from Yokohama City University
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Understanding the mechanism by which hormone refractory prostate cancer (HRPC) develops remains a major issue. Alterations in HRPC include androgen receptor (AR) changes. In addition, the AR is activated by cytokines such as interleukin-6 (IL-6). Atypical protein kinase C (aPKC lambda/iota) has been implicated in the progression of several cancers. Herein, we provide evidence that aPKC lambda/iota expression correlates with prostate cancer recurrence. Experiments in vitro and in vivo revealed aPKC lambda/iota to be involved in prostate cancer cell growth through secretion of IL-6. Further, aPKC lambda/iota activates transcription of the IL-6 gene through NF kappa B and AP-1. We conclude that aPKC lambda/iota promotes the growth of hormone independent prostate cancer cells by stimulating IL-6 production in an autocrine manner. Our findings not only explain the link between aPKC lambda/iota and IL-6, implicated in the progression a variety of cancers, but also establish a molecular change involved in the development of HRPC. Further, aPKC lambda/iota expression might be a biomarker for prostate cancer progression.
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