Endocrine Abstracts

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...

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...

Raised levels of IGF-I have been associated with risk of developing several cancers including breast carcinoma. In addition to promoting mitogenesis in breast cancer cells, a number of observations suggest a role for inhibition of apoptosis by IGF-I receptor activation. Ligand binding to IGF-IR leads to activation of both the phosphoinositide-3'-kinase (PI3K) and the Ras/Raf/MAPKinase pathways. Deprivation of serum growth factors induces apoptosis in MCF-7 breast cancer cells ...

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...

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...

Prostate and breast cancers remain common causes of cancer related deaths in the UK. The majority of cases appear to be of a multifactorial aetiology that includes a genetic component. It has been suggested that low levels of circulating 1,25 dihydroxyvitamin D3 are associated with an increased risk of both breast and prostate cancer. A number of polymorphisms in the vitamin D receptor (VDR) gene have been identified resulting in differing genotypes that may alter s...