Journal
BMC CANCER
Volume 10, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1471-2407-10-142
Keywords
-
Categories
Funding
- American Cancer Society [IRG-112367]
- NIH [P01 CA95426, P30 CA16058, CA84402, K24 CA93670, K22 CA134551]
- Melanoma Research Foundation
- Harry J. Lloyd Charitable Trust
- Valvano Foundation for Cancer Research
Ask authors/readers for more resources
Background: Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells. Methods: Basal and interferon-alpha (IFN-alpha) or interferon-gamma (IFN-gamma)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr(701)-phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR. Results: SOCS1 and SOCS3 proteins were expressed at basal levels in melanocytes and in all melanoma cell lines examined. Expression of the SOCS1 and SOCS3 proteins was also enhanced following stimulation of a subset of cell lines with IFN-alpha or IFN-gamma. Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr(701)-phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-alpha (IFIT2, OAS-1, ISG-15) or IFN-gamma (IRF1). Conversely, siRNA inhibition of SOCS1 and SOCS3 expression in melanoma cells enhanced their responsiveness to interferon stimulation. Conclusions: These data demonstrate that SOCS proteins are expressed in human melanoma cell lines and their modulation can influence the responsiveness of melanoma cells to IFN-alpha and IFN-gamma.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available