Endocrine Abstracts

Background: Ghrelin was recently discovered as the natural ligand for the G protein-coupled growth hormone secretagogue receptor and induces GH release through GHS-R1a. The octanoylation of its third serine residue is responsible for GH release and receptor binding. A variant of ghrelin devoid of this modification, desoctanoyl-ghrelin, can neither bind to the receptor nor induce GH release. Ghrelin has also been shown to effect cellular proliferation, being pro-proliferative i...

Background: Tamoxifen is a partial estrogen agonist used to treat estrogen receptor positive breast cancer. It has been discovered however that resistance to tamoxifen develops in some cancers. In order to investigate the mechanisms underlying the development of resistance we have created a tamoxifen resistant breast cancer cell line.Aims: To develop a breast cancer cell line that is resistant to the anti-growth effects of tamoxifen.<p class="abstext...

Background: The pro-proliferative and anti-apoptotic IGF-I is implicated in the development of colorectal cancer (CRC) in both the general population and patients with acromegaly. The local intracolonic environment is also likely to be important, particularly unconjugated bile acids such as deoxycholic acid (DCA). Whilst low faecal concentrations may be proliferative, high levels are toxic to colonic epithelial cells.High levels of DCA have been linked t...

Background. Recent studies have linked high serum levels of IGF-1 and low levels of IGFBP-3 with an increased risk of colorectal cancer. BP3 has been shown to have IGF-1 independent effects on cell proliferation in breast and prostate cells, but its effects on colon cancer cells is largely unknown. Aims. To determine: 1) the effects of BP-3 on colonic epithelial cell proliferation and apoptosis, and 2) whether any effects are independent of IGF-1. Methods....

Background: The growth hormone/ IGF-I axis is important in the pathogenesis of breast cancer and increased IGF-I signalling through the IGF-I receptor (IGF-IR) has been implicated in the development of tamoxifen resistance in breast cancer.Aims: To compare mRNA and protein expression of IGF-I & IGF-IR in (i) wild type (WT) and tamoxifen resistant (TR) MCF-7 breast cancer cells and (ii) breast cancer tissue from women with primary and recurrent, tamox...

Background: Due to its cross-talk with estrogen receptor (ER) signalling, increased IGF-I signalling through the IGF-I receptor (IGF-IR) has been postulated as an important factor in the development of tamoxifen resistance in breast cancer.Aims: To investigate the importance of IGF-I signalling in tamoxifen resistant (TR) and wild-type (WT) MCF-7 breast cancer cells by (i) assessing cell proliferation in response to IGF-I and tamoxifen and (ii) using sma...

Introduction: The development of colorectal cancer is influenced by dietary as well as growth factors. Butyrate, (NaB) one of the metabolic by-products of bacterial fermentation of dietary fibre is a primary source of energy for colonic mucosa. It has growth-promoting effects on normal colonic epithelial cells, induces cell cycle arrest, differentiation and apoptosis in colorectal cancer cells. Since it has been suggested that the apoptotic effects of NaB may be due to its syn...

Cannabinoids and ghrelin are potent appetite stimulators. The ghrelin receptor (GHS-R1a), endocannabinoids and the cannabinoid 1 (CB1) receptor are expressed in the hypothalamus. There is evidence that the novel CB1 antagonist, rimonabant, causes weight loss by both central and peripheral effects. The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status and regulates the energy metabolism within the single cell but also at whole body level. We have shown p...

Introduction:Hepatic IGF-I is generally believed to be regulated by pituitary-derived GH. However recent studies have emphasized the importance of paracrine/autocrine IGF-I in normal growth and development, as well as some malignancies. However, it remains unclear how locally produced IGF-I is regulated. The aim of this project was to investigate IGF-I expression in different tissues from the growth hormone receptor knock-out (GHR-KO) mouse.<p class=...

Introduction: The GH/IGF-I axis has been implicated in the pathogenesis of breast cancer and development of tamoxifen resistance. We have previously used siRNA to successfully silence the IGF-I receptor (IGF-IR) in MCF-7 breast cancer cells. To further characterize the growth changes that occur when elements of the GH/IGF-I axis are disrupted we investigated the use of siRNA to cause long term silencing of IGF-IR.Methods: MCF-7 cells were cultured in phe...