Searchable abstracts of presentations at key conferences in endocrinology

ea0009oc37 | Oral Communication 5: Thyroid | BES2005

PTTG Binding Factor (PBF) - a novel transforming gene in thyroid tumorigenesis which represses iodide uptake

Stratford A , Boelaert K , Tannahill L , Eggo M , Gittoes N , Franklyn J , McCabe C

We have previously shown PTTG binding factor (PBF) to be a transforming gene both in vitro and in vivo, forming colonies in soft agar and tumours in nude mice. We have found that along with PTTG, PBF is upregulated in thyroid cancer and is also a prognostic indicator for recurrence. As our cohort of thyroid cancers showed significantly reduced sodium iodide symporter (NIS) expression compared to normal thyroid (47% reduction, N=27, P=0.005), which was negatively ...

ea0003oc34 | Hormone Action | BES2002

Iodothyronine deiodinase expression in thyroid responsive fetal tissues

Chan S , Kachilele S , McCabe C , Tannahill L , Boelaert K , Gittoes N , Franklyn J , Kilby M

The critical role of thyroid hormones (TH) in normal human growth and fetal development is well recognised. The availability of tri-iodothyronine (T3) to bind to thyroid hormone receptors is determined by the local concentrations of T3, as well as the local action of deiodinase enzymes that determine conversion of T4.Quantitative real time RT-PCR was used to quantify the expression of mRNAs encoding the specific deiodinase subtypes (D1, D2 & D3) in h...

ea0003p284 | Thyroid | BES2002

Pituitary tumor transforming gene and basic fibroblast growth factor-2 - novel potential molecular indicators for thyroid cancer

Boelaert K , McCabe C , Tannahill L , Gittoes N , Eggo M , Watkinson J , Sheppard M , Franklyn J

Differentiated thyroid cancers are the commonest endocrine malignancies, but there are no reliable molecular markers of prognosis. Pituitary tumor transforming gene (PTTG) plays several potential roles in tumour initiation and progression, including regulating mitosis and stimulating expression of fibroblast growth factor-2 (FGF-2). PTTG expression has been identified as a potential prognostic marker in pituitary adenomas and colon carcinomas. We postulated that PTTG and FGF-2...

ea0009oc36 | Oral Communication 5: Thyroid | BES2005

PTTG Induces Genomic Instability in Thyroid Cells

Kim D , Stratford A , Boelaert K , Pemberton H , Gockce C , Eggo M , Tannahill L , Watkinson J , Franklyn J , McCabe C

Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Differentiated thyroid cancers exhibit aneuploidy; cytogenetic studies have demonstrated the importance of genetic instability in thyroid cancer development. Pituitary tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and over-exp...

ea0009p148 | Thyroid | BES2005

Gene regulation by the c-terminal pxxp motif of pituitary tumor transforming gene (PTTG)

Gokce C , Tannahill L , Stratford A , Khanim F , Pemberton H , Kim D , Gittoes N , Boelaert K , Franklyn J , McCabe C

PTTG is tumourigenic in vivo and transactivates fibroblast growth factor-2 (FGF-2). We have previously identified expression of PTTG and FGF-2 as potential prognostic indicators for differentiated thyroid cancer. Critical to PTTG function is a double PXXP motif, forming a putative SH3-interacting domain. We employed cDNA array approaches to identify further genes regulated via this region. MCF12A cells were transiently transfected with vector-only (VO) control, wild-type (WT)-...

ea0007oc10 | Development and growth | BES2004

Key mitotic regulators securin and separase in the human fetal brain

Boelaert K , Pemberton H , Kim D , Tannahill L , Chan S , Khanim F , Gittoes N , Franklyn J , Kilby M , McCabe C

Human securin, also known as pituitary tumor transforming gene, plays a critical role during cell division. Ubiquitination of securin during the metaphase to anaphase transition releases its binding partner separase, which cleaves the cohesins holding sister chromatids together. We recently demonstrated reduced securin expression in human fetal versus adult brain, and dissected its role in affecting the proliferation of human embryonal CNS precursor NTERA-2 (NT-2) cells. We ha...

ea0005p164 | Growth and Development | BES2003

A potential role for human securin/PTTG in the developing human fetal brain

Boelaert K , McCabe C , Tannahill L , Bulmer J , Chan S , Gittoes N , Sheppard M , Kilby M , Franklyn J

Human securin, known also as pituitary tumor transforming gene (PTTG), has established oncogenic and cell regulatory functions. PTTG transforms cells in vitro, inhibits sister chromatid separation and regulates secretion of fibroblast growth factor-2 (FGF-2). FGF-2 is a key regulator of CNS development and PTTG/securin expression has previously been reported in murine fetal brain. We examined mRNA and protein expression of PTTG and FGF-2 in 35 first trimester (7-12 weeks) and ...

ea0003oc13 | Endocrine Neoplasia | BES2002

Disruption of the SH3 domain of pituitary tumor transforming gene (PTTG) reveals distinct mechanisms of FGF-induction and cell transformation

Boelaert K , Tannahill L , McRobbie L , Moore J , Young L , Sheppard M , Franklyn J , Gittoes N , McCabe C

PTTG transforms cells in vitro, is tumourigenic in vivo and regulates secretion of fibroblast growth factor-2 (FGF-2). Critical to transactivation of FGF-2 is PTTG's SH3 interacting domain which encodes the gene's sole phosphorylation site. We explored the mechanisms through which PTTG stimulates FGF-2 expression and cell transformation using specific mutations resulting in unphosphorylated PTTG (phos-), a mimic of constitutive phosphorylation (phos+), and a disr...

ea0003oc14 | Endocrine Neoplasia | BES2002

Expression and function of vascular endothelial growth factor (VEGF) and its receptor KDR in pituitary tumours

McCabe C , Boelaert K , Tannahill L , Khaira J , McRobbie L , Hussain S , Sheppard M , Gittoes N , Franklyn J

Pituitary tumourigenesis is a complex and poorly understood process. Crucial to the initiation and growth of such tumours is the oncogene PTTG, which stimulates FGF-2-mediated angiogenesis. We recently investigated expression of the angiogenic factor VEGF and its receptor KDR in 103 pituitary tumours. Non-functioning tumours demonstrated markedly raised VEGF mRNA (3.2-fold, P<0.05) and protein levels compared to normal pituitaries (N=10). KDR was also highly induced in NFTs...

ea0003p139 | Endocrine Tumours and Neoplasia | BES2002

The destruction box of pituitary tumor transforming gene (PTTG) mediates cell transformation

McCabe C , Horwitz G , Tannahill L , Boelaert K , Yu R , McRobbie L , Sheppard M , Franklyn J , Gittoes N

PTTG has a dual role in tumorigenesis. Firstly, it regulates expression of basic fibroblast growth factor (FGF-2), and secondly, as a human securin homologue, it inhibits sister chromatid separation in mitosis. Securins must be degraded at Destruction Box (DB) motifs by an anaphase promoting complex (APC), before cell division can proceed. We have used a variety of approaches to examine the precise roles of the PTTG Destruction Box and FGF-2 stimulation in cell transformation....