Protein Kinase Cε Interacts with Signal Transducers and Activators of Transcription 3 (Stat3), Phosphorylates Stat3Ser727, and Regulates Its Constitutive Activation in Prostate Cancer
| Autor: | Dawn R. Church, Herbert Manoharan, Terry D. Oberley, Ajit K. Verma, Weixiong Zhong, Nancy E. Dreckschmidt, Moammir H. Aziz, George Wilding |
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| Rok vydání: | 2007 |
| Předmět: |
Male
STAT3 Transcription Factor Cancer Research Transcription Genetic Protein Kinase C-epsilon Biology Transfection Mice Prostate cancer DU145 Cell Line Tumor LNCaP Serine medicine Animals Humans Neoplasm Invasiveness Phosphorylation STAT3 Protein kinase A Prostatic Neoplasms Cancer medicine.disease Mice Inbred C57BL Oncology biology.protein Cancer research Cytokines Adenocarcinoma Signal transduction Signal Transduction |
| Zdroj: | Cancer Research. 67:8828-8838 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-07-1604 |
| Popis: | Prostate cancer is the most common type of cancer in men and ranks second only to lung cancer in cancer-related deaths. The management of locally advanced prostate cancer is difficult because the cancer often becomes hormone insensitive and unresponsive to current chemotherapeutic agents. Knowledge about the regulatory molecules involved in the transformation to androgen-independent prostate cancer is essential for the rational design of agents to prevent and treat prostate cancer. Protein kinase Cε (PKCε), a member of the novel PKC subfamily, is linked to the development of androgen-independent prostate cancer. PKCε expression levels, as determined by immunohistochemistry of human prostate cancer tissue microarrays, correlated with the aggressiveness of prostate cancer. The mechanism by which PKCε mediates progression to prostate cancer remains elusive. We present here for the first time that signal transducers and activators of transcription 3 (Stat3), which is constitutively activated in a wide variety of human cancers, including prostate cancer, interacts with PKCε. The interaction of PKCε with Stat3 was observed in human prostate cancer, human prostate cancer cell lines (LNCaP, DU145, PC3, and CW22rv1), and prostate cancer that developed in transgenic adenocarcinoma of mouse prostate mice. In reciprocal immunoprecipitation/blotting experiments, prostatic Stat3 coimmunoprecipitated with PKCε. Localization of PKCε with Stat3 was confirmed by double immunofluorescence staining. The interaction of PKCε with Stat3 was PKCε isoform specific. Inhibition of PKCε protein expression in DU145 cells using specific PKCε small interfering RNA (a) inhibited Stat3Ser727 phosphorylation, (b) decreased both Stat3 DNA-binding and transcriptional activity, and (c) decreased DU145 cell invasion. These results indicate that PKCε activation is essential for constitutive activation of Stat3 and prostate cancer progression. [Cancer Res 2007;67(18):8828–38] |
| Databáze: | OpenAIRE |
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