aPKCλ/ι promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6

• Published in: Proceedings of the National Academy of Sciences - PNAS 2009, Vol.106 (38), p.16369-16374
• Main Authors: Ishiguro, Hitoshi, Akimoto, Kazunori, Nagashima, Yoji, Kojima, Yasuyuki, Sasaki, Takeshi, Ishiguro-Imagawa, Yukari, Nakaigawa, Noboru, Ohno, Shigeo, Kubota, Yoshinobu, Uemura, Hiroji
• Format: Article
• Language: English
• Subjects: androgen receptors; autocrine signaling; biomarkers; cell growth; genes; in vitro studies; interleukin-6; neoplasm cells; prostatic neoplasms; protein kinase C; secretion; somatotropin; transcription factor NF-kappa B; transcriptional activation
• ISSN: 0027-8424; 1091-6490

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 (aPKCλ/ι) has been implicated in the progression of several cancers. Herein, we provide evidence that aPKCλ/ι expression correlates with prostate cancer recurrence. Experiments in vitro and in vivo revealed aPKCλ/ι to be involved in prostate cancer cell growth through secretion of IL-6. Further, aPKCλ/ι activates transcription of the IL-6 gene through NFκB and AP-1. We conclude that aPKCλ/ι 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 aPKCλ/ι and IL-6, implicated in the progression a variety of cancers, but also establish a molecular change involved in the development of HRPC. Further, aPKCλ/ι expression might be a biomarker for prostate cancer progression.