Abstract | BACKGROUND: METHODS: Parental LNCaP cells and an LNCaP-IL6+ subline, derived from parental LNCaP cells by continuous culture of the cells in the presence of recombinant IL-6 were used in the study. Expression of STAT3, pSTAT3, ERK, pERK, AKT, pAKT, PTEN, and SHP-1 was analyzed by immunohistochemistry, Western blots, cDNA microarray, quantitative PCRs, and reverse transcriptase PCRs. Proliferation and apoptosis of transfected cells were analyzed by caspase3/7 assay and flow cytometry. RESULTS: Phosphorylation of ERK and STAT3 was increased in the LNCaP-IL6+ subline compared with LNCaP cells, whereas pAKT was decreased. Overexpression and inhibition experiments with SHP-1 siRNA showed that SHP-1 reduced proliferation and increased apoptosis in both cell lines. Microarray analysis revealed 80 up-regulated and 87 down-regulated SHP-1-related genes in the LNCaP-IL6+ cell line compared with LNCaP cells. CONCLUSIONS: SHP-1 suppresses growth and increases apoptosis in both LNCaP and LNCaP-IL6+ cells, which suggests that SHP-1 could be a therapeutic target in prostate cancer, even when there is an IL-6-related growth advantage.
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Authors | Helena Tassidis, Zoran Culig, Anette Gjörloff Wingren, Pirkko Härkönen |
Journal | The Prostate
(Prostate)
Vol. 70
Issue 14
Pg. 1491-500
(Oct 01 2010)
ISSN: 1097-0045 [Electronic] United States |
PMID | 20687222
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | (c) 2010 Wiley-Liss, Inc. |
Chemical References |
- DNA Primers
- Interleukin-6
- STAT3 Transcription Factor
- Extracellular Signal-Regulated MAP Kinases
- Protein Tyrosine Phosphatase, Non-Receptor Type 6
- PTEN Phosphohydrolase
- PTEN protein, human
- Caspase 3
- Caspase 7
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Topics |
- Caspase 3
(metabolism)
- Caspase 7
(metabolism)
- Cell Division
- Cell Line, Tumor
- DNA Primers
- Disease Progression
- Down-Regulation
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Humans
- Immunohistochemistry
(methods)
- Interleukin-6
(physiology)
- Kinetics
- Lymphatic Metastasis
(genetics, pathology)
- Male
- PTEN Phosphohydrolase
(genetics)
- Prostatic Neoplasms
(enzymology, genetics, pathology, physiopathology)
- Protein Tyrosine Phosphatase, Non-Receptor Type 6
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- STAT3 Transcription Factor
(metabolism)
- Up-Regulation
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