Expression of Pituitary Tumor Transforming Gene (PTTG) and its binding protein in human astrocytes and astrocytoma cells: Function and regulation of PTTG in U87 astrocytoma cells

TY - JOUR

T1 - Expression of Pituitary Tumor Transforming Gene (PTTG) and its binding protein in human astrocytes and astrocytoma cells

T2 - Function and regulation of PTTG in U87 astrocytoma cells

AU - Tfelt-Hansen, Jacob

AU - Yano, Shozo

AU - Bandyopadhyay, Sanghamitra

AU - Carroll, Rona

AU - Brown, Edward M.

AU - Chattopadhyay, Naibedya

PY - 2004/9/1

Y1 - 2004/9/1

N2 - Human securin, pituitary tumor transforming gene (PTTG), is a protooncogene. Here we report expressions of PTTG and its interacting protein, PTTG-binding factor in human astrocytic cells. PTTG expression was higher in malignant cells than in primary astrocytes, whereas PTTG-binding factor was not. Using a xenotransplantable, glioma cell line (U87), we observed that knocking down PTTG mRNA by RNA silencing inhibited serum-induced proliferation by approximately 50%. Furthermore, in U87 cells PTTG expression was up-regulated by promalignant ligands epithelial growth factor (EGF) and TGFα, both at the protein and mRNA levels. PTTG induction by EGF receptor (EGFR) ligands could be blocked by the specific EGFR inhibitor, AG1478. Hepatocyte growth factor (HGF) also induced PTTG but to a lesser extent than EGF. Although EGF stimulates HGF secretion in U87 cells, the effect of EGF on PTTG mRNA expression is independent of HGF as neutralizing antibody against HGF failed to abolish EGF-induced up-regulation of PTTG mRNA. PTTG mRNA was unchanged by incubating U87 cells with the promalignant growth factor TGFβ, apoptosis inducing TNFα and ligands for nuclear receptors, such as retinoic acid and retinoid X receptors and peroxisome proliferator-activated receptor-γ, known for their growth-inhibitory and apoptosis-inducing effects on gliomas. In addition, 17β-estradiol and Ca2+, known to activate PTTG expression, did not change PTTG mRNA levels in U87 cells. In summary, we show higher PTTG expression in astrocytoma than normal astrocytes and secondly, PTTG is involved in glioma cell growth. Finally, regulation of its espression has glioma-specific features and is selectively regulated by promalignant cytokines including EGFR ligands and HGF.

AB - Human securin, pituitary tumor transforming gene (PTTG), is a protooncogene. Here we report expressions of PTTG and its interacting protein, PTTG-binding factor in human astrocytic cells. PTTG expression was higher in malignant cells than in primary astrocytes, whereas PTTG-binding factor was not. Using a xenotransplantable, glioma cell line (U87), we observed that knocking down PTTG mRNA by RNA silencing inhibited serum-induced proliferation by approximately 50%. Furthermore, in U87 cells PTTG expression was up-regulated by promalignant ligands epithelial growth factor (EGF) and TGFα, both at the protein and mRNA levels. PTTG induction by EGF receptor (EGFR) ligands could be blocked by the specific EGFR inhibitor, AG1478. Hepatocyte growth factor (HGF) also induced PTTG but to a lesser extent than EGF. Although EGF stimulates HGF secretion in U87 cells, the effect of EGF on PTTG mRNA expression is independent of HGF as neutralizing antibody against HGF failed to abolish EGF-induced up-regulation of PTTG mRNA. PTTG mRNA was unchanged by incubating U87 cells with the promalignant growth factor TGFβ, apoptosis inducing TNFα and ligands for nuclear receptors, such as retinoic acid and retinoid X receptors and peroxisome proliferator-activated receptor-γ, known for their growth-inhibitory and apoptosis-inducing effects on gliomas. In addition, 17β-estradiol and Ca2+, known to activate PTTG expression, did not change PTTG mRNA levels in U87 cells. In summary, we show higher PTTG expression in astrocytoma than normal astrocytes and secondly, PTTG is involved in glioma cell growth. Finally, regulation of its espression has glioma-specific features and is selectively regulated by promalignant cytokines including EGFR ligands and HGF.

UR - http://www.scopus.com/inward/record.url?scp=4344683429&partnerID=8YFLogxK

U2 - 10.1210/en.2003-1661

DO - 10.1210/en.2003-1661

M3 - Journal article

C2 - 15178645

AN - SCOPUS:4344683429

SN - 0013-7227

VL - 145

SP - 4222

EP - 4231

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 9

ER -