Endocrine Abstracts

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...

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...

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...

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: IGF-1 is a ubiquitous growth factor that has been shown to play an important role in breast tissue development and tumorigenesis. Previously we have shown that IGF-1 expression is lost in approximately 1/3 of breast carcinomas. It is unsure whether this indicates the existence of a subset of breast cancers that may behave differently clinically and on a molecular level. Aims: To assess and quantify the mRNA expression of (i) Cox-2 and c-myc, genes imp...