TY - JOUR
T1 - Different signalling pathways regulate VEGF and IL-8 expression in breast cancer
T2 - Implications for therapy
AU - Chelouche Lev, Dina
AU - Miller, Claudia P.
AU - Tellez, Carmen
AU - Ruiz, Maribelis
AU - Bar-Eli, Menashe
AU - Price, Janet E.
N1 - Funding Information:
The work was supported in part by DAMD-17-00-1-0315 and DAMD17-02-1-0455 from the US Army Medical Research and Materiel Command (J.E.P), an award from the Texas Higher Education Coordinating Board (J.E.P.), National Cancer Institute Grant CA76098 (M.B.-E.) and Cancer Center Support Core Grant CA16672.
PY - 2004/11
Y1 - 2004/11
N2 - Elevated expression of pro-angiogenic cytokines is associated with aggressive tumour growth and decreased survival of patients with breast cancer. In general, the breast cancer cell lines with high vascular endothelial growth factor (VEGF) expression also express high levels of interleukin-8 (IL-8). The consequence of inhibiting mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K), both implicated in regulation of these cytokines, was examined in four cell lines. Treatment with the mitogen-activated protein kinase/extracellular signal-related kinase (MEK) inhibitor U0126 reduced expression of VEGF and IL-8 in MDA-MB-231 cells, partially inhibited expression in MDA-MB-468 and Hs578T cells, with minimal effects in GI101A cells. Treatment with LY294002 reduced cytokine expression in GI101A and MDA-MB-468 cells, with partial reduction in Hs578T and less effect in MDA-MB-231 cells. Thus, IL-8 and VEGF were regulated by different signalling pathways in different cell lines; this suggests that inhibition of the dominantly active pathway can downregulate both angiogenic cytokines. Recognising which signalling pathway is active may identify targets for anti-angiogenic therapy of breast cancer.
AB - Elevated expression of pro-angiogenic cytokines is associated with aggressive tumour growth and decreased survival of patients with breast cancer. In general, the breast cancer cell lines with high vascular endothelial growth factor (VEGF) expression also express high levels of interleukin-8 (IL-8). The consequence of inhibiting mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K), both implicated in regulation of these cytokines, was examined in four cell lines. Treatment with the mitogen-activated protein kinase/extracellular signal-related kinase (MEK) inhibitor U0126 reduced expression of VEGF and IL-8 in MDA-MB-231 cells, partially inhibited expression in MDA-MB-468 and Hs578T cells, with minimal effects in GI101A cells. Treatment with LY294002 reduced cytokine expression in GI101A and MDA-MB-468 cells, with partial reduction in Hs578T and less effect in MDA-MB-231 cells. Thus, IL-8 and VEGF were regulated by different signalling pathways in different cell lines; this suggests that inhibition of the dominantly active pathway can downregulate both angiogenic cytokines. Recognising which signalling pathway is active may identify targets for anti-angiogenic therapy of breast cancer.
KW - Angiogenic cytokines
KW - Breast cancer
KW - Mitogen-activated protein kinase
KW - Phosphatidylinositol-3-kinase
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U2 - 10.1016/j.ejca.2004.05.024
DO - 10.1016/j.ejca.2004.05.024
M3 - Article
C2 - 15519527
AN - SCOPUS:7044234484
SN - 0959-8049
VL - 40
SP - 2509
EP - 2518
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 16
ER -