کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5514808 1541689 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Endothelin causes transactivation of the EGFR and HER2 in non-small cell lung cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Endothelin causes transactivation of the EGFR and HER2 in non-small cell lung cancer cells
چکیده انگلیسی


- ET-1 addition to NSCLC cells causes tyrosine phosphorylation of the EGFR, HER2 and ERK.
- ET-1 binds with high affinity to NSCLC and causes elevated cytosolic Ca2+ which is blocked by the ETAR antagonists BQ123 and ZD4054.
- The ability of ET-1 to cause EGFR and HER2 transactivation is blocked by ETAR antagonists and gefitinib, a tyrosine kinase inhibitor.
- ET-1 stimulates the growth of NSCLC cells, whereas ETAR antagonists and gefitinib inhibit NSCLC proliferation.

Endothelin (ET)-1 is an important peptide in cancer progression stimulating cellular proliferation, tumor angiogenesis and metastasis. ET-1 binds with high affinity to the ETA receptor (R) and ETBR on cancer cells. High levels of tumor ET-1 and ETAR are associated with poor survival of lung cancer patients. Here the effects of ET-1 on epidermal growth factor (EGF)R and HER2 transactivation were investigated using non-small cell lung cancer (NSCLC) cells. ETAR mRNA was present in all 10 NSCLC cell lines examined. Addition of ET-1 to NCI-H838 or H1975 cells increased EGFR, HER2 and ERK tyrosine phosphorylation within 2 min. The increase in EGFR and HER2 transactivation caused by ET-1 addition to NSCLC cells was inhibited by lapatinib (EGFR and HER2 tyrosine kinase inhibitor (TKI)), gefitinib (EGFR TKI), ZD4054 or BQ-123 (ETAR antagonist), GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor) or Tiron (superoxide scavenger). ET-1 addition to NSCLC cells increased cytosolic Ca2+ and reactive oxygen species. ET-1 increased NSCLC clonal growth, whereas BQ123, ZD4054, lapatinib or gefitinib inhibited proliferation. The results indicate that ET-1 may regulate NSCLC cellular proliferation in an EGFR- and HER2-dependent manner.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 90, April 2017, Pages 90-99
نویسندگان
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