Endocrine Abstracts

Studies in vitro have highlighted the potent anti-cancer effects of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3). However, the in vivo application of 1,25D3 and its synthetic analogs remains problematical due to persistent hypercalcaemic side-effects. Recent studies have shown that it may be possible to overcome this in an autocrine fashion via extra-renal synthesis of 1,25D3. In particular, analysis of prostate and co...

2-Methoxyoestrogens are emerging as a new class of anti-neoplastic agents. 2-Methoxyoestradiol (2-MeOE2), an endogenous oestrogen metabolite, has shown anti-proliferative effects in ER+ve and ER-ve breast cancer cell lines. In this study we have investigated the effects of sulphamoylated derivatives of 2-MeOE2, 2-methoxyoestradiol-3-O-monosulphamate (2-MeOE2MATE) and 2-methoxyoestradiol 3,17 bis sulphamate (2-MeOE2bisMATE) in ER-ve MDA-MB-231 cells. Both 2-MeOE2MATE and 2-MeOE...

We hypothesised that normal regulation of 25(OH)D3-24-hydroxylase (encoded by CYP24) determines the autocrine/paracrine action of 1,25(OH)2D3 in normal breast and prostate epithelial cells. Furthermore, these processes are compromised in malignancy.We therefore studied the regulation of CYP24, amongst a panel of breast and prostate cancer cell lines (ZR-75-1, T47-D, MCF-7, MDA-MB-231 breast cells and LNCaP, PC-3 and DU-145 prostate cells) that display d...

Ghrelin, the natural ligand for the GHS-R, modulates proliferation in cell lines derived from malignant breast tissue. It has been suggested that this action is independent of the GHS-R. We have previously demonstrated that MCF7 cells expressed ghrelin but not GHS-R mRNA and MDA-MB231 cells expressed GHS-R but not ghrelin mRNA. To determine whether ghrelin modulates proliferation in MCF7 and MDA-MB231 cells we performed proliferation assays treating with saline, 1 and 10nM ghr...

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...

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...

Background: Acromegalics are at increased risk of developing colorectal neoplasia with an increase of right-sided disease. Several genes are implicated in colorectal neoplasia including components of the GH/IGF-1 axis. It is unclear whether regional variations in neoplasia are explained by variations in local expression of these genes. Aims: To compare the expression of the components of the GH/IGF-1 axis and other putative genes between the left and right colon of patients wi...

Diazoxide is an agonist of ATP sensitive K+ (KATP) channels in beta-cells and is used in the treatment of hyperinsulinism caused by insulinomas or Hyperinsulinism in Infancy (HI). The responsiveness of patients to diazoxide is highly variable and complicated by side-effects which include hypertension and hypertrichosis. The aim of this study was to examine the actions of a novel benzothiadiazine-derivative, BPDZ-154, on beta-cell KATP channels and insulin release. W...