Tumor growth suppressive effect of IL-4 through p21-mediated activation of STAT6 in IL-4Rα overexpressed melanoma models.

Abstract

To evaluate the significance of interleukin 4 (IL-4) in tumor development, we compared B16F10 melanoma growth in IL-4-overespressing transgenic mice (IL-4 mice) and non-transgenic mice. In IL-4 mice, reduced tumor volume and weight were observed when compared with those of non-transgenic mice. Significant activation of DNA binding activity of STAT6, phosphorylation of STAT6 as well as IL-4, IL-4Rα and p21 expression were found in the tumor tissues of IL-4 mice compared to non-transgenic mice. Higher expression of IL-4, STAT6 and p21 in human melanoma tissue compared to normal human skin tissue was also found. Higher expression of apoptotic protein such as cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax, p53 and p21, but lower expression levels of survival protein such as Bcl-2 were found in the tumor of IL-4 mice. In vitro study, we found that overexpression of IL-4 significantly inhibited SK-MEL-28 human melanoma cell and B16F10 murine melanoma cell growth via p21-mediated activation of STAT6 pathway as well as increased expression of apoptotic cell death proteins. Moreover, p21 knockdown with siRNA abolished IL-4 induced activation of STAT6 and expression of p53 and p21 accompanied with reduced IL-4 expression as well as melanoma cell growth inhibition. Therefore, these results showed that IL-4 overexpression suppressed tumor development through p21-mediated activation of STAT6 pathways in melanoma models.

• Authors: Hye Lim Lee, Mi Hee Park, Ju Kyoung Song, Yu Yeon Jung, Youngsoo Kim, Kyung Bo Kim, Dae Yeon Hwang, Do Young Yoon, Min Jong Song, Sang Bae Han, Jin Tae Hong
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 17 Pg. 23425-38 (Apr 26 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26993600 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• IL4 protein, human
• IL4R protein, human
• Interleukin-4 Receptor alpha Subunit
• STAT6 Transcription Factor
• STAT6 protein, human
• Interleukin-4

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Proliferation
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Disease Models, Animal
• Female
• Humans
• Interleukin-4 (genetics, metabolism)
• Interleukin-4 Receptor alpha Subunit (genetics, metabolism)
• Male
• Melanoma (genetics, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Transgenic
• Prognosis
• STAT6 Transcription Factor (genetics, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays