Endocrine Abstracts

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: 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: Serum IGF-I and IGFBP-3 levels respectively have a positive and negative association with subsequent risk of breast cancer. The anti-oestrogen tamoxifen is widely used as adjunctive therapy after resection of primary breast tumours. Tamoxifen has been reported to influence serum IGF-I, although its effects on BP-3 are unknown. The effects of tumour resection itself on IGF-I and BP-3 levels are unclear.Aims: To determine the effects of surgery...

Introduction: Somatostatin and its analogues (SSA) have been reported to have anti-proliferative effects. We have recently demonstrated expression of all 5 somatostatin receptor sub-types in normal and malignant colonic tissue. SOM-230 (Novartis) is a novel SSA that has a wider binding affinity to somatostatin receptors compared to octreotide (OCT). Its effects on proliferation of colonic cancer cells are unknown.Aims: To determine the effects of SOM-230...

Background: The GH/IGF-I axis has been implicated in the development of breast cancer. However the regulation of local expression of the GH/IGF-I axis in breast tissue is unknown. In vitro studies have suggested an inhibitory effect of ghrelin on the proliferation of breast cancer cell lines, although the mechanisms for this action are unknown.Aims: Using a physiologically relevant culture system for breast tissue explants, to investigate the effects of ...