Document Detail


Growth differentiation factor-15 upregulates interleukin-6 to promote tumorigenesis of prostate carcinoma PC-3 cells.
MedLine Citation:
PMID:  22872134     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Growth differentiation factor-15 (GDF15), a member of TGF-β superfamily, is associated with human cancer progress. We evaluated the role of GDF15 plays in tumorigenesis of prostate carcinoma PC-3 cells. Results from real-time reverse transcription-polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) revealed that expression of GDF15 was approximately 3-fold higher in LNCaP cells than in PC-3 cells. Other prostate cell lines (PZ-HPV-7, CA-HPV-10, and DU145 cells) expressed extremely low levels of GDF15. Stable overexpression of GDF15 in PC-3 cells enhanced the degree of cell proliferation and invasion as shown respectively in the 3H-thymidine incorporation assay and the matrigel invasion assay. Soft agar assays and xenograft animal studies indicated that overexpression of GDF15 in PC-3 cells increased tumorigenesis in vitro and in vivo. Results from RT-PCR, immunoblot, and reporter assays revealed that overexpression of GDF15 resulted in decreased expression of maspin and upregulation of interleukin-6 (IL-6), matriptase, and N-myc downstream-regulated gene 1 (Ndrg1) expression. Further studies revealed that overexpression of IL-6 enhanced GDF15 expression in LNCaP cells while knockdown of IL-6 blocked the expression of GDF15 in PC-3 cells, suggesting that expression of GDF15 is upregulated by IL-6. This study demonstrated that expression of GDF15 induces cell proliferation, invasion, and tumorigenesis of prostate carcinoma PC-3 cells. The enhancement of tumorigenesis and invasiveness of prostate carcinoma cells that stably overexpress GDF15 may be caused by the dysregulation of maspin, matriptase, and IL-6 gene expression. The expression of GDF15 and IL-6 is controlled via a positive feedback loop in PC-3 cells.
Authors:
Ke-Hung Tsui; Ying-Ling Chang; Tsui-Hsia Feng; Li-Chuan Chung; Tzu-Yi Lee; Phei-Lang Chang; Horng-Heng Juang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-7
Journal Detail:
Title:  Journal of molecular endocrinology     Volume:  -     ISSN:  1479-6813     ISO Abbreviation:  J. Mol. Endocrinol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8902617     Medline TA:  J Mol Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
K Tsui, Urology, Chang Gung Memorial Hospital, Kwei-Shan, Taiwan.
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