Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens

Int J Cancer. 2010 Oct 1;127(7):1625-36. doi: 10.1002/ijc.25182.


We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1beta. This effect is NF-kappaB and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1beta reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1alpha or IL-1beta secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that approximately 13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cell Line, Tumor
  • Cytokines / immunology
  • Down-Regulation
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-1alpha / metabolism
  • Interleukin-1alpha / pharmacology*
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology*
  • MAP Kinase Kinase 4 / antagonists & inhibitors
  • MAP Kinase Kinase 4 / metabolism
  • Melanocytes / cytology*
  • Melanocytes / immunology
  • Melanoma / genetics
  • Melanoma / immunology*
  • Microphthalmia-Associated Transcription Factor / genetics*
  • NF-kappa B / immunology
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology


  • Cytokines
  • Interleukin-1alpha
  • Interleukin-1beta
  • Microphthalmia-Associated Transcription Factor
  • NF-kappa B
  • RNA, Messenger
  • MAP Kinase Kinase 4