AIM: The aim of the present study was to explore the role of receptor tyrosine kinases (RTKs) in the regulation of expression of PTX-3, a protector in atherosclerosis. METHODS: Human monocytic U937 cells were infected with a shRNA lentiviral vector library targeting human RTKs upon LPS stimuli and PTX-3 expression was determined by ELISA analysis. The involvement of downstream signaling in the regulation of PTX-3 expression was analyzed by both Western blotting and ELISA assay. RESULTS: We found that knocking down of ERBB2/3, EPHA7, FGFR3 and RET impaired PTX-3 expression without effects on cell growth or viability. Moreover, inhibition of AKT, the downstream effector of ERBB2/3, also reduced PTX-3 expression. Furthermore, we showed that FGFR3 inhibition by anti-cancer drugs attenuated p38 activity, in turn induced a reduction of PTX-3 expression. CONCLUSION: Altogether, our study demonstrates the role of RTKs in the regulation of PTX-3 expression and uncovers a potential cardiotoxicity effect of RTK inhibitor treatments in cancer patients who have symptoms of atherosclerosis or are at the risk of atherosclerosis.
AIM: The aim of the present study was to explore the role of receptor tyrosine kinases (RTKs) in the regulation of expression of PTX-3, a protector in atherosclerosis. METHODS:Human monocytic U937 cells were infected with a shRNA lentiviral vector library targeting human RTKs upon LPS stimuli and PTX-3 expression was determined by ELISA analysis. The involvement of downstream signaling in the regulation of PTX-3 expression was analyzed by both Western blotting and ELISA assay. RESULTS: We found that knocking down of ERBB2/3, EPHA7, FGFR3 and RET impaired PTX-3 expression without effects on cell growth or viability. Moreover, inhibition of AKT, the downstream effector of ERBB2/3, also reduced PTX-3 expression. Furthermore, we showed that FGFR3 inhibition by anti-cancer drugs attenuated p38 activity, in turn induced a reduction of PTX-3 expression. CONCLUSION: Altogether, our study demonstrates the role of RTKs in the regulation of PTX-3 expression and uncovers a potential cardiotoxicity effect of RTK inhibitor treatments in cancerpatients who have symptoms of atherosclerosis or are at the risk of atherosclerosis.
Authors: M M Luchetti; G Piccinini; A Mantovani; G Peri; C Matteucci; G Pomponio; M Fratini; P Fraticelli; P Sambo; C Di Loreto; A Doni; M Introna; A Gabrielli Journal: Clin Exp Immunol Date: 2000-01 Impact factor: 4.330
Authors: D J Slamon; B Leyland-Jones; S Shak; H Fuchs; V Paton; A Bajamonde; T Fleming; W Eiermann; J Wolter; M Pegram; J Baselga; L Norton Journal: N Engl J Med Date: 2001-03-15 Impact factor: 91.245
Authors: Michael S Rolph; Sabine Zimmer; Barbara Bottazzi; Cecilia Garlanda; Alberto Mantovani; Göran K Hansson Journal: Arterioscler Thromb Vasc Biol Date: 2002-05-01 Impact factor: 8.311
Authors: F Breviario; E M d'Aniello; J Golay; G Peri; B Bottazzi; A Bairoch; S Saccone; R Marzella; V Predazzi; M Rocchi Journal: J Biol Chem Date: 1992-11-05 Impact factor: 5.157