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. 2015 Jun 29;35(11):1411–1422. doi: 10.1038/onc.2015.199

Figure 1.

Figure 1

PKA inhibition significantly abrogated p75NTR-induced glioma invasion. (a) Treatment with increasing concentrations of the PKA inhibitor KT5720 (KT) inhibited invasion of U87 cells expressing full-length p75NTR (p75). Following pre-treatment with KT5720 for 1 h, the invasive ability of the U87 cells expressing full-length p75NTR (p75) or empty vector (pcDNA; control) were determined using collagen-coated transwells. Similar results were observed in two independent experiments. Asterisk (*) indicate P<0.05 and double asterisks (**) indicate P<0.01 versus non-treated U87p75 cells (one-way ANOVA with the Newman-Keuls post-test). (b) Highly invasive U87R and noninvasive U87T cells were isolated by serial in vivo selection and assessed for their invasive ability in the absence or presence of KT5720 (200 nM). Asterisks (***) indicate P<0.001 as compared with non-treated cells. (c) Western blot shows the expression of p75NTR in patient-derived glioma cells BT042, BT147 and BT134. (d) Histogram shows that the invasion of the patient-derived glioma cells (BTIC) in the presence of fetal bovine serum was suppressed by KT5720 (200 nM). Asterisks (**) indicate P<0.01 as compared with the corresponding non-treated BTIC. (e) p75NTR-mediated glioma invasion is dependent on cAMP. U87pcDNA or p75 cells were treated for 1 h with an adenylyl cyclase inhibitor (2', 5'-dideoxyadenosine(2', 5'-ddA)) and invasion assays (described above) were performed. Asterisk (**) indicate P<0.01 versus non-treated U87p75 cells. (f) U87p75NTR treated with the PKA inhibitor KT5720 (1 h, 200 nM), 2', 5'-ddA (1 h, 30 μM) or the adenylyl cyclase activator forskolin (1 μM) in the presence or absence of 2', 5'-ddA were assessed for cAMP activity using a CRE-luciferase reporter construct. Histogram shows the fold increases in luciferase activity as compared with vehicle-treated cells. Asterisk (**) indicate P<0.01 versus non-treated U87p75 cells. Data represent the mean±s.e.m. of triplicates, representative of at least three independent experiments.