Endocrine Abstracts

During mitosis, temporal release of separase from its inhibitor securin results in cohesin cleavage, thereby promoting anaphase. The developing fetal brain has rapidly proliferating neuronal cells whilst adult neurons no longer proliferate. When comparing 61 fetal and 12 adult human brain samples, we found significantly increased separase mRNA and protein throughout ontogeny and reduced securin expression in fetal brain compared with adult. Using MTT assays, we examined the ef...

During early development, the extravillous and villous placenta form by a process of proliferation and differentiation resulting in invasion of the uterine decidua and myometrium. The invasion of tissues during placentation is a model for the proliferative and invasive processes which occur during tumourogenesis. Pituitary tumor transforming gene (PTTG) interacts with a binding factor PBF, and PTTG expression correlates with tumor invasiveness in many neoplasms. We hypothesise...

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...

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...