Tumor Growth Suppressive Effect of IL-4 Through p21-Mediated Activation of STAT6 in IL-4Rα Overexpressed Melanoma Models

Authors

Hye Lim Lee, Chungbuk National University, South Korea
Mi Hee Park, Chungbuk National University, South Korea
Ju Kyoung Song, Chungbuk National University, South Korea
Yu Yeon Jung, Chungbuk National University, South Korea
Youngsoo Kim, Chungbuk National University, South Korea
Kyung Bo Kim, University of KentuckyFollow
Dae Yeon Hwang, Pusan National University, South Korea
Do Young Yoon, Konkuk University, South Korea
Min Jong Song, The Catholic University of Korea, South Korea
Sang Bae Han, Chungbuk National University, South Korea
Jin Tae Hong, Chungbuk National University, South Korea

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.

Document Type

Article

Publication Date

3-16-2016

Notes/Citation Information

Published in Oncotarget, v. 7, no. 17, p. 23425-23438.

Licensed under a Creative Commons Attribution 3.0 License.

This article has been corrected. Oncotarget. 2017; 8:41778. https://doi.org/10.18632/oncotarget.18561. It is available for download as an additional file.

Digital Object Identifier (DOI)

https://doi.org/10.18632/oncotarget.8111

Funding Information

This work was supported by the National Research Foundation of Korea [NRF] grant funded by the Korea government [MEST] (MRC, 2011–0028213).

Repository Citation

Lee, Hye Lim; Park, Mi Hee; Song, Ju Kyoung; Jung, Yu Yeon; Kim, Youngsoo; Kim, Kyung Bo; Hwang, Dae Yeon; Yoon, Do Young; Song, Min Jong; Han, Sang Bae; and Hong, Jin Tae, "Tumor Growth Suppressive Effect of IL-4 Through p21-Mediated Activation of STAT6 in IL-4Rα Overexpressed Melanoma Models" (2016). Pharmaceutical Sciences Faculty Publications. 74.
https://uknowledge.uky.edu/ps_facpub/74