Searchable abstracts of presentations at key conferences in endocrinology

ea0009p84 | Endocrine tumours and neoplasia | BES2005

DNA array analysis of a vitamin D-resistant variant of MCF-7 breast cancer cells

Townsend K , Colston K , Bujalska I , Campbell M , Hewison M

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3) is a potent antiproliferative agent with putative applications in the treatment of common cancers. However, doses of 1,25D3 required to achieve tangible anticancer responses also stimulate unwanted calciotropic effects. Data suggest that this is due, in part, to acquired resistance to 1,25D3 in cancer cells, particularly in more aggressive tumours. To investigate this fu...

ea0007oc3 | Reproduction | BES2004

Decidual activation of vitamin D3 - a novel immunomodulatory mechanism in early gestation

Evans K , Innes B , Bulmer J , Kilby M , Hewison M

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3) is a potent antiproliferative/immunomodulatory steroid hormone with many applications outside calcium homeostasis. This is particularly true in the placenta which can generate 1,25D3 locally via the enzyme 1alpha-hydroxylase (CYP27b) in both trophoblast and decidua. We have investigated the potential function of 1,25D3 across gestation using human tissue obtained after l...

ea0007oc23 | Endocrine tumours | BES2004

Expression of vitamin D metabolism and signalling components in breast tumours compared to paired normals

Townsend K , Guy M , Colston K , Mansi J , Campbell M , Hewison M

Recent studies have highlighted a role for vitamin D in the prevention and treatment of breast cancer. The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is a potent antiproliferative/proapoptotic agent and its nuclear receptor (vitamin D receptor, VDR) is well expressed in breast tissue. We have investigated whether or not VDR signalling in breast tumours is due to systemic (renal) 1,25D3 or, as with oestrogens, there is local sy...

ea0003oc9 | Endocrine Neoplasia | BES2002

Breast cancer cells express the vitamin D activating enzyme 1alpha-hydroxylase

Townsend K , Evans K , Hughes S , Mork|#Hansen C , Colston K , Campbell M , Hewison M

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...

ea0003p146 | Endocrine Tumours and Neoplasia | BES2002

Inhibition of 11beta-HSD2 has an anti-proliferative effect on pituitary tumour cells

Rabbitt E , Bujalska I , Stewart P , Sheppard M , Hewison M , Gittoes N

The physiological effects of glucocorticoids (GCs) are, at least in part, mediated by an inhibition of cell proliferation. More contentious is their anti-proliferative action and possible tumour modifying effects in neoplastic tissues. Central to the action of GCs in target tissues is the expression and function of two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) that serve to interconvert active cortisol (F) and inactive cortisone (E). 11beta-HSD type 1 (11bet...

ea0003p227 | Reproduction | BES2002

Increased HOXA10 expression in late gestation: A novel target for hormonal regulation in placenta and decidua

Evans K , Driver P , Zehnder D , Bulmer J , Stewart P , Kilby M , Hewison M

Homeobox (HOX) genes encode proteins that are important in normal foetal development. Some of these genes such as HOXA10 also appear to be involved in haematopoiesis, tumour invasion and normal uterine function. HOXA10 is sensitively regulated by hormonal changes during the menstrual cycle. In addition, knockout mouse studies have suggested a role for HOXA10 in implantation but its precise mechanism of action remains unclear. To further investigate HOXA10 function in human rep...

ea0003p244 | Steroids | BES2002

Expression and corticosteroid regulation of serum and glucocorticoid regulated kinase, and epithelial sodium channel subunits in human ocular ciliary epithelium

Rauz S , Walker E , Hughes S , Coca-Prados M , Hewison M , Murray P , Stewart P

Sodium transport across the human ocular non-pigmented ciliary epithelium (NPE) is fundamental to the production aqueous humour and maintenance of intraocular pressure. In sodium transporting tissues, serum and glucocorticoid regulated kinase isoform 1 (SGK1) has been identified as an early corticosteroid target gene in the activation of pre-existing epithelial sodium channels (ENaC). We previously demonstrated the presence of both the mineralocorticoid (MR) and glucocorticoid...

ea0006s20 | The endocrinologist and bone | SFE2003

11beta-hydroxysteroid dehydrogenase type 1: a prereceptor regulator of glucocorticoids in bone

Hewison|M##Cooper|P##Stewart M

Glucocorticoids have potent but paradoxical effects on bone. In vitro they are required for the differentiation of osteoblasts but in excess can cause suppression of the mature osteoblast phenotype by reducing proliferation and inducing apoptosis. In vivo, glucocorticoids are anabolic at physiological concentrations, but in excess have an adverse effect on the skeleton most clearly seen in steroid-induced osteoporosis. We have postulated that this paradox may be ...

ea0005p116 | Endocrine Tumours and Neoplasia | BES2003

Dysregulated extra-renal synthesis of 1,25-dihydroxyvitamin D3: A novel cause of hypercalcemia associated with ovarian dysgerminomas

Evans K , Zehnder D , Kilby M , Taylor H , Hewison M

Hypercalcaemia is a prevalent complication in malignancies as a consequence of tumor secretion of parathyroid hormone related peptide (PTHrP). This complication is also associated with ovarian dysgerminomas but is much less common than for other tumours. To investigate this further we have studied 10 cases of dysgerminoma, assessing biochemical parameters and analysing mRNA and protein expression in tissue biopsies. Pathological reports show raised serum calcium and 1,25(OH)<s...

ea0005p128 | Endocrine Tumours and Neoplasia | BES2003

CYP27b and CYP24 expression combine to determine 1,25 Dihydroxyvitamin D3 insensitivity in breast cancer cells

Townsend K , Banwell C , Stewart P , Hewison M , Campbell M

To dissect mechanisms which result in 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) insensitivity we have compared the antiproliferative actions of 1,25(OH)2D3 in a range of malignant breast cell lines (ZR-75-1, T-47D, MCF-7, MCF-7Res and MDA-MB-231) and the non-malignant breast epithelial cells MCF-12A cells. All the malignant cell lines displayed greater resistance than MCF-12A cells to 1,25(OH)2D3. For ex...