aPKClambda/iota promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6.
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 (aPKClambda/iota) has been implicated in the progression of several cancers. Herein, we provide evidence that aPKClambda/iota expression correlates with prostate cancer recurrence. Experiments in vitro and in vivo revealed aPKClambda/iota to be involved in prostate cancer cell growth through secretion of IL-6. Further, aPKClambda/iota activates transcription of the IL-6 gene through NFkappaB and AP-1. We conclude that aPKClambda/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 aPKClambda/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, aPKClambda/iota expression might be a biomarker for prostate cancer progression.
Ishiguro
Hitoshi
H
Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
Akimoto
Kazunori
K
Nagashima
Yoji
Y
Kojima
Yasuyuki
Y
Sasaki
Takeshi
T
Ishiguro-Imagawa
Yukari
Y
Nakaigawa
Noboru
N
Ohno
Shigeo
S
Kubota
Yoshinobu
Y
Uemura
Hiroji
H
D000368:Aged; D019898:Autocrine Communication; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D000099293:Protein Kinase C-lambda
D015850:Interleukin-6; D007527:Isoenzymes; D016328:NF-kappa B; D011493:Protein Kinase C; D018808:Transcription Factor AP-1; D000099293:Protein Kinase C-lambda