Endocrine Abstracts

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...

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=...

Background: There is considerable evidence to support a role for the GH/IGF-I axis in the development of breast cancer. We have previously demonstrated that IGF-I is expressed in both normal and malignant breast tissue, but that approximately 10% of primary breast cancers reveal no IGF-I mRNA expression. However the molecular differences between IGF-I positive and IGF-I negative tumours is unknown.Aims: To investigate the molecular differences between IG...

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: Vitamin D prevents proliferation, promotes differentiation and induces apoptosis of colonic cells. A reduced dietary intake is associated with an increased risk of colorectal cancer (CRC). Recently, we have shown that 25-hydroxyvitamin D-1-alpha hydroxylase (1aOHase) mRNA, which converts vitamin D to its active metabolite, is upregulated in CRC. However, this was based on small number of samples and data on vitamin D receptor (VDR) expression in CRC are inconsisten...

Background: Sporadic colorectal carcinoma (CRC) is more common on the left side of the colon. Acromegaly confers an increased risk of developing CRC but with an increase of right sided disease. IGFBP-3 both regulates tissue exposure to IGF-I and also exerts cellular IGF-l independent pro-apoptotic effects. Whether variation in regional IGFBP-3 expression in the colon may explain the observed pattern of disease in both normal and acromegalic patients is unknown.Aim: 1) To c...

Background: Previously we have demonstrated expression of GH, IGF-1 and ghrelin, but not GHRH, in normal and malignant breast tissue. In vitro studies have suggested an inhibitory effect of ghrelin on proliferation of breast cancer cell lines. However the use of cell lines and dose of ghrelin may not represent physiological conditions.Objectives: (1) To establish a viable method for culturing fresh breast tissue explants, (2) to use this to investigate t...

Background: Recent studies have suggested that an increased level of serum IGF-1 and a decreased level of IGFBP-3 may be associated with an increased risk of developing subsequent breast cancer. However, it is uncertain whether these effects are mediated solely by endocrine actions or whether local effects might also be important. We have previously demonstrated IGF-1 mRNA to be universally expressed in normal breast tissue but in only 50% of cancers. The expression of IGFBP-3...

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...