Endocrine Abstracts

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: Previous studies have implicated the GH/IGF-I axis in the pathogenesis of breast cancer and the development of tamoxifen resistance. IGF-I is a known proliferative and anti-apoptotic agent. In order to characterize the growth changes that occur when elements of the GH/IGF-I axis are disrupted we have used siRNA to transcriptionally silence the IGF-IR in the MCF-7 human breast cancer cell line.Methods: MCF-7 cells were cultured in phenol red-f...

IntroductionIncreased cross talk between the IGF-I and oestrogen signalling pathways has been implicated in the development of tamoxifen resistance in breast cancers. We have previously demonstrated IGF-I mRNA to be down-regulated in primary breast cancers. However, the expression of IGF-I and IGFBP-3 in recurrent, tamoxifen-resistant tumours is unknown.MethodsTotal RNA was extracted from 38 paired samples of...

IntroductionIncreased cross talk between the IGF-I and oestrogen signalling pathways has been implicated in the development of tamoxifen resistance in breast cancers. We have previously demonstrated IGF-I mRNA to be down-regulated in primary breast cancers. However, the expression of IGF-I and IGFBP-3 in recurrent, tamoxifen-resistant tumours is unknown.MethodsTotal RNA was extracted from 38 paired samples of primary breast cancers (T) and adjacent normal (N) tissue and from 1...

BackgroundIn addition to inhibiting pituitary GH secretion, somatostatin (SS) and its analogues have been shown to exert anti-proliferative effects on a variety of different cell types. The presence of receptors for SS have been demonstrated in a number of tissues but quantification of mRNA expression of the 5 subtypes of SSTR in the colon is unknown.MethodsTotal RNA was extracted from 9 paired samples of adj...

Background:Recent studies have linked low serum levels of IGFBP-3 with an increased risk of developing breast cancer.In addition to modulating IGF-I bioactivity, IGFBP-3 also exerts IGF-I independent pro-apoptotic effects. Our previous work has demonstrated that IGFBP-3 mRNA expression is significantly down regulated in breast tumours compared to normal breast tissue. It is uncertain, however, how this pattern of expression relates to the pathological and prognostic features o...

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...

Introduction: The GH/IGF-I axis is implicated in colorectal cancer development. We have previously shown regional variations of the GH/IGF-I axis, and other tumour associated genes between the rectum (RS) and caecum (C). Whether variations in the GH/IGF-I axis align with differing expression patterns is unknown.Aim: To determine the association between colonic expression of the GH/IGF-I axis and that of tumour associated genes by region.<p class="abs...

Background. The GH/IGF-I axis has been implicated in the pathogenesis of colon and breast cancer. We have recently demonstrated that the local expression of its components correlates with that of tumour-associated genes and angiogenesis. The two predominant isomers of GH in humans are 22kDa and 20kDa isomers. A recent study reported that the two isomers exert opposing effects on breast cancer cells: 22kDa GH promotes proliferation whereas 20kDa GH inhibits proliferation. The l...

Background: The growth hormone/ insulin-like growth factor-1 (GH/IGF-1) axis has been increasingly implicated in the pathogenesis of breast cancer. We have recently demonstrated the local expression of both GH and IGF-I in normal and malignant breast tissue. However, the regulation of this local GH/IGF-1 expression is unknown. Aims: (i) To quantify the mRNA levels of GHRH, ghrelin and their receptors in malignant and adjacent normal breast tissue, and (ii) to determine any cor...