Ets1 transcription factor mediates gastrin-releasing peptide-induced IL-8 regulation in neuroblastoma cells.

Angiogenesis plays a critical role in tumor progression in various cancers, including neuroblastoma. We have previously shown that gastrin-releasing peptide (GRP) stimulates neuroblastoma growth and that its cell surface receptors, gastrin-releasing peptide receptors (GRP-R), are overexpressed in advanced-stage human neuroblastomas; however, the effects of GRP on angiogenesis are not clearly elucidated. Interleukin (IL) 8, a proinflammatory chemokine, plays an important role during tumor angiogenesis.

Gastrin-releasing peptide-induced down-regulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten) in neuroblastomas.

Objectives: To evaluate whether aggressive, undifferentiated neuroblastomas express tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten) and to examine the effects of gastrin-releasing peptide (GRP) on PTEN gene and protein expression.

Summary Background Data: We have previously shown that neuroblastomas secrete GRP, which binds to its cell surface receptor (GRP-R) to stimulate cell growth in an autocrine fashion. However, the effects of GRP on expression of the tumor suppressor gene PTEN have not been elucidated in neuroblastomas.

Ets transcriptional regulation of gastrin-releasing peptide receptor in neuroblastomas.

Background: We have demonstrated that gastrin-releasing peptide (GRP) binds specifically to its cell surface receptor, GRP-R, to act as an autocrine/paracrine growth factor for neuroblastomas (NBs); an increased expression of GRP-R was found in more advanced-stage NBs. Ets family proteins are nuclear targets for intracellular kinase pathways that can lead to cell proliferation; however, a potential role of Ets in the expression of GRP-R in NBs is unknown. Therefore, the purpose of our study was to determine whether Ets regulates transcriptional activity of GRP-R in NBs.