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

• DOI: 10.1073/pnas.0907044106
• Publication Date: 2009-09-03T02:00:35Z
• Authors: Hitoshi Ishiguro; Kazunori Akimoto; Yoji Nagashima; Yasuyuki Kojima; Takeshi Sasaki; Yukari Ishiguro-I...; Noboru Nakaigawa; Shigeo Ohno; Yoshinobu Kubota; Hiroji Uemura
• Keywords: Male; 0301 basic medicine; Interleukin-6; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; NF-kappa B; Prostatic Neoplasms; Enzyme-Linked Immunosorbent Assay; Kaplan-Meier Estimate; Immunohistochemistry; 3. Good health; Gene Expression Regulation, Neoplastic; Isoenzymes; Autocrine Communication; 03 medical and health sciences; Cell Line, Tumor; Disease Progression; Humans; RNA Interference; Neoplasm Recurrence, Local; Protein Kinase C; Aged; Cell Proliferation

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.