Endocrine Abstracts

Chromosomal instability (CIN) is a common feature of many malignancies including papillary and follicular thyroid cancer. During mitosis, there are multiple stages which, if dysregulated, may result in CIN. One critical stage is the regulation of sister-chromatid separation at the metaphase-anaphase transition. Three key protein complexes regulate this process: separase, cohesins and securin (also known as pituitary tumor transforming gene). In vivo, most tumours studied demon...

Thyroid hormones are essential for optimum fetal neurodevelopment. In-utero nutrition is dependant on adequate placentation. Epidermal growth factor (EGF) and hepatocyte growth factor (HGF) have been demonstrated to affect proliferation of human trophoblast and may therefore play a role in adequate human placentation. Intrauterine growth restriction (a process associated with malplacentation) is associated with fetal hypothyroxinemia and enhanced thyroid receptor (TR) expressi...

PTTG has been implicated in the pathogenesis of pituitary, thyroid and other tumours. PBF was recently identified as a protein which interacts specifically with PTTG both in vitro and in vivo. PBF facilitates PTTG's nuclear localisation, and mediates its ability to transactivate basic fibroblast growth factor (FGF-2). We investigated PBF expression and function in vitro, and examined its relationship to PTTG action. Transient transfection of wild type PTTG induced a significan...

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)-...

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...