aPKC lambda/iota promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6

作者：Ishiguro Hitoshi; Akimoto Kazunori; Nagashima Yoji; Kojima Yasuyuki; Sasaki Takeshi; Ishiguro Imagawa Yukari; Nakaigawa Noboru; Ohno Shigeo; Kubota Yoshinobu; Uemura Hiroji^*

来源：Proceedings of the National Academy of Sciences, 2009, 106(38): 16369-16374.

DOI：10.1073/pnas.0907044106

• IL-6
• PSA
• recurrence

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.

• 出版日期2009-9-22