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

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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 nontransgenic 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.

Original languageEnglish
Pages (from-to)23425-23438
Number of pages14
JournalOncotarget
Volume7
Issue number17
DOIs
StatePublished - Apr 26 2016

Bibliographical note

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

Keywords

  • IL-4
  • Melanoma
  • P21
  • STAT6
  • Tumor growth

ASJC Scopus subject areas

  • Oncology

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