Endocrine Abstracts

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Two industrial PCB mixtures, Aroclors 1221 and 1254 have been suggested to have estrogenic and anti-estrogenic properties, respectively. We have examined whether these PCB mixtures modulated bone formation and resorption in intact and ovariectomized (ovx) rat models. Twentyfour adult female rats were divided into three groups subcutaneously receiving 4% DMSO (Control), Aroclor 1221 (10 mg/kg) and Aroclor...

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...

The cell cycle occupies a pivotal role in the control of cellular proliferation, a critical point being activation of CyclinE which is held in check by the inhibitor p27. CyclinE is targeted for degradation by the F-box protein Archipelago (Ago/Fbw7/cdc4), while p27 is exported out of the nucleus by Jun activation domain-binding protein 1 (Jab1). Over-expression of CyclinE has been reported in breast cancer. We have now explored the role of Jab1 and Ago in mediating changes in...

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...

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...

Background:The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis has been increasingly implicated in the development of breast cancer. Previously we have demonstrated the local expression of IGF-I in normal and malignant breast tissue. However the correlation of this local expression with clinical factors has not fully been investigated.Aims: (i) To quantify the mRNA levels of IGF-I in normal and malignant breast tissue and (ii) to identify any correlation betwee...

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: 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...