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Dissertation
IL-10 signal transduction and its influence on prostate cells
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania and Hahnemann University
Sep 1999
DOI:
https://doi.org/10.17918/00008653
Abstract
Interleukin-10 (IL-10) is a cytokine whose many functions have attracted wide attention from immunologists and cancer researchers. One area that has not been investigated was the role of IL-10 in prostate cancer. Surprisingly, we discovered that IL-10 stimulated human PC-3 ML prostate cancer cell proliferation, indicating it may play an important role in the regulation of cell growth and/or survival. Following IL-10 treatment, differential RNA display analysis revealed that IL-10 upregulated follistatin production in PC-3 ML cells. Follistatin binds to activin, a growth inhibitory molecule, to support cell survival. We have examined whether IL-10, follistatin or activin play an important role in the growth and cell survival of primary prostate cell lines derived from normal, benign and malignant prostate tissues. IL-10 and follistatin independently stimulated the proliferation of these three cell lines. Activin failed to support cell growth and flow-cytometry cell cycle analysis showed that activin induced apoptosis in these cells. IL-10 and Follistatin both blocked activin's apoptotic effects. Many studies have suggested that IL-10 activated STAT signaling controls gene expression in human macrophages and B cells. In contrast, our studies revealed that IL-10 down regulated STAT 1 and STAT 3 signaling in PC-3 ML cells, indicating a novel IL-10 signaling pathway might be involved in control gene expression in prostate cells (i.e. follistatin). In sum, the work reported in this thesis has shown for the first time that IL-10 regulates follistatin expression in prostate cells. The mechanism of action of IL-10 is unknown, but may involve down regulation of STAT 1 and STAT 3 expression. This study also revealed, a novel autocrine/paracrine regulation system (follistatin and activin) and IL-10 might regulate cell growth and apoptosis in prostate cells.
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Details
- Title
- IL-10 signal transduction and its influence on prostate cells
- Creators
- Anjiang Liu
- Contributors
- Mark E. Stearns (Advisor) - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Awarding Institution
- Medical College of Pennsylvania and Hahnemann University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania and Hahnemann University; Philadelphia, Pennsylvania
- Number of pages
- xii, 88 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Other Identifier
- 991021889010304721