Hilary R. Glover

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Currently available antioestrogens, such as tamoxifen, are competitive inhibitors that bind to the ligand binding sites of oestrogen receptors, ERalpha and ERbeta. The search for alternative anti-hormone therapies is prompted by the need for drugs that are effective when tumours become tamoxifen resistant. The existence of different receptor isoforms also(More)
4-Hydroxy tamoxifen (OHT) and trilostane interact differently with the oestrogen receptor (ER). OHT is a competitive inhibitor whereas trilostane has direct, but non-competitive effects on ER. This study compared the effects of OHT and trilostane, in the presence of 17beta-oestradiol (E2) on gene expression in MCF-7 breast cancer cells using microarrays(More)
Therapies designed to treat hypercortisolism have usually sought to reduce circulating glucocorticoid concentrations, however the local tissue endocrine environment could be an alternative target. The 3beta-hydroxysteroid dehydrogenase Delta5-4 isomerase (3beta-HSD) inhibitor trilostane is of interest, since, although it is only moderately and transiently(More)
Interaction with the src family of tyrosine kinases is crucial to the transforming action of polyomavirus middle T-antigen (MT). Association with MT activates the tyrosine kinase activity of pp60(c-src) and, through subsequent MT phosphorylation, creates binding sites for signalling molecules whose stimulation culminates in cell transformation. Despite this(More)
Polymoma virus encodes a potent oncogene, the middle T-antigen (MT), that induces cell transformation by copying the actions of tyrosine kinase associated growth factor receptors. A crucial component of MT transformation is its ability to bind and stimulate the activity of src-family kinases. However, the mechanism by which this is achieved remains unclear.(More)
FDC-P1 haemopoietic cells were used to select mutations of c-fms that constitutively activate the receptor for macrophage-colony stimulating factor (M-CSF or CSF-1). One mutation changed Ser 929 to Gly within a Ser/Gly rich region of the C-terminal tail and a second changed a nearby, highly conserved Leu 926 for Pro. A third mutation (D802V) changed Asp 802(More)
ShcA and Grb2 are crucial components in signalling by most tyrosine kinase-associated receptors. How ever, it is not clear whether Grb2 bound directly to the receptor is equivalent to Grb2 associated via ShcA. We have used signalling stimulated by the middle T-antigen (MT) of polyoma virus to address this question. The two known Grb2-binding sites from(More)
Several lines of evidence attest to the existence of alternative ligand binding sites on the oestrogen receptor (ER), including non-competitive inhibition by trilostane or tamoxifen. It is possible that the inhibitory action of conventional oestrogen agonists at high concentrations may indicate that they too interact at alternative ER sites, albeit at low(More)
Stem cell factor (SCF) was found to stimulate the growth of the haemopoietic cell line FDC-P1 in synergy with either interleukin 3 (IL-3) or granulocyte-macrophage-colony stimulating factor (GM-CSF). Similarly, macrophage colony-stimulating factor (M-CSF) was shown to synergize with IL-3 or GM-CSF, following the infection of FDC-P1 cells with a recombinant(More)
647 Background: Activating protein-1 (AP1) elements in gene promoters are pivotal in growth factor mediated cell survival pathways in breast cancer. Selective estrogen receptor modulators are known to alter estrogen receptor (ER) conformation giving rise to differential gene activation through estrogen response elements (EREs) and AP1 elements. Trilostane(More)
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