Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) is one of the key regulators of tumor neoangiogenesis. It acts through two types of high-affinity tyrosine kinase receptors (VEGF receptor-1 [VEGFR-1]/fms-related tyrosine kinase 1 [Flt-1] and VEGFR-2/kinase domain receptor [KDR]) expressed on endothelial cells. VEGFRs have also been detected on cancer cells, suggesting a possible autocrine effect of VEGF on their growth. We studied the expression of VEGF, VEGFR-1, and VEGFR-2 in human medulloblastoma cell lines (DAOY, D283Med, and D341Med) and investigated the possible autocrine mechanisms of VEGF on medulloblastoma cell proliferation. Reverse transcriptase PCR analysis showed the presence of VEGF and VEGFR mRNAs in all cell lines studied. Of the three VEGF isoforms, VEGF(121) and VEGF(189) were detected by Western blot analysis in all three medulloblastoma cell lines, whereas VEGF(165) was identified only in DAOY cells. Medulloblastoma cell lines expressed both VEGFR-1 and VEGFR-2. We also demonstrated expression of VEGF and its receptors in medulloblastoma tumor specimens. Exogenous VEGFR-2 inhibitor reduced the VEGF-dependent cell proliferation of DAOY and D283Med cells. In DAOY cells, VEGF(165) induced phosphorylation of VEGFR-2/KDR and of downstream proteins in the signal transduction pathway. These data suggest a possible autocrine role for VEGF in medulloblastoma growth. Targeting VEGF signaling may represent a new therapeutic option in the treatment of medulloblastoma.
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PMID:Functional VEGF and VEGF receptors are expressed in human medulloblastomas. 1770 59

Medulloblastoma is one of the common malignant brain tumors in children or young adults and its overall disease-free 5-year survival rate is approximately 50% due to tumor progression, invasion, and metastasis. This study aimed to determine whether one of Rho GTPases, Rac1 can affect the morphology, motility, and invasion of medulloblastoma cells through knockdown of Rac1 expression. Medulloblastoma Daoy cells were used to manipulate Rac1 expression using Rac1 shRNA, Rac1N17, and Rac1L61 constructs. Reverse transcriptase-PCR and western blot were used to detect expression of Rac1 mRNA and protein, respectively. Invasion and migration assays were performed to assess invasion and migration capacity of Daoy cells, respectively. The data showed that Rac1 mRNA and protein were overexpressed in Daoy cells. Deletion of Rac1 decreased the cross-linked actin network and pseudopodia and also inhibited the number of migration cells migrated or invaded to the other side of the filter compared to control cells. These data indicated that the invasion and migration in Daoy cells were inhibited by deletion of Rac1, and suggest that targeting Rac1 by Rac1 shRNA may further be evaluated and used as a potential anticancer strategy to treat medulloblastoma.
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PMID:Inhibition of tumor cell migration and invasion through knockdown of Rac1 expression in medulloblastoma cells. 2107 38