Activation of RET tyrosine kinase regulates interleukin-8 production by multiple signaling pathways

Naoko Iwahashi, Hideki Murakami, Yuji Nimura, Masahide Takahashi

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Interleukin-8 (IL-8) is known to contribute to human cancer progression through its potential function as a mitogenic, angiogenic, or motogenic factor. We found a high level of IL-8 production in SK-N-MC human primitive neuroectodermal tumor cells transfected with the human RET gene (SK-N-MC (RET) cells) in response to glial cell line-derived neurotrophic factor (GDNF) stimulation. IL-8 was also produced at high levels in TT human medullary thyroid carcinoma and TPC-1 human papillary thyroid carcinoma cell lines both of which express activated RET tyrosine kinase. To investigate which signaling pathways are responsible for IL-8 expression, we treated SK-N-MC (RET) cells with several kinase inhibitors before GDNF stimulation. The results showed that a MEK1 inhibitor, PD98059, a p38MAPK inhibitor, SB202190, and a protein kinase C (PKC) inhibitor, Calphostin C, markedly decreased the IL-8 secretion from SK-N-MC (RET) cells at 24 h after GDNF stimulation. In contrast, a phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002, increased its secretion. These results thus suggested that IL-8 production by RET tyrosine kinase is regulated by multiple signaling pathways.

Original languageEnglish
Pages (from-to)642-649
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 14-06-2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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