Endocrine Abstracts

Fenretinide (4-hydroxyphenyl retinamide, 4-HPR) is a synthetic retinoid that exhibits anti-neoplastic properties and clinical trials indicate a potential chemopreventative action of 4HPR in the development of ovarian cancer. Although the mechanism of 4HPR action remains largely unknown, ceramide has been recently proposed as a cellular signal.The aim of the present study is to investigate in vitro the action of 4HPR and the retinoic acid receptor ...

In our in-vitro experiments we examined the involvement of insulin-like growth factor type II (IGF-II) in the control of ovarian function in domestic fowl, together with the intracellular mechanisms of IGF-II action. Fragments of ovarian follicles were cultured with and without IGF-II (1-100 ng/ml), blockers of protein kinase A (PAK, KT5820, 10 mg/ml), tyrosine kinase (TK, AG1024, 1mg/ml), mitogen-activated protein konase (MAPK, PD98059, 10 mg/ml), cyclin-dependent protein kin...

BACKGROUND: Ghrelin is a novel 28-amino acid peptide which was isolated from the rat stomach and has now been shown to have a widespread tissue distribution. Ghrelin is the endogenous ligand of the growth hormone secretagogue receptor type 1a (GHS-R1a), and stimulates growth hormone (GH) release via the hypothalamus as well as by a direct action on the pituitary GHS-R1a. Ghrelin and the GHS-R1a also coexist within the pituitary. There are conflicting data regarding the effects...

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...

It has been reported that Ang II induces the growth of MCF-7 breast cancer cells (Muscella et al., J Endocrinol 173, 315-323, 2002). Here we have examined the signalling pathways evoked by Ang II in MCF-7. Ang II did not change the concentration of intracellular calcium but induced the cytosol-to-membrane translocation of atypical protein kinase C zeta (PKC-zeta). Ang II dose-dependently induced c-fos (mRNA and protein) and enhanced the phosphorylation state of extracellular s...

The insulin-like growth factors together with the IGF receptors, IGFBPs and IGFBP proteases are involved in the regulation of somatic growth and cellular proliferation in vivo and in vitro. Our previous studies demonstrated that overexpression of IGFBP-2 in colon cancer cells (Caco-2) was associated with increased cell proliferation and tumorigenesis. The wild-type Caco-2 cells express and secrete IGFBP-2, IGFBP-4, IGF1R and growth hormone receptors but not IGFBP-3. Therefore,...

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...