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Title: Oestrogen action in human ovarian cancer
Author: Hirst, Gillian Louise
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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The aims of this study were to examine the role of oestrogen in a series of ER-positive ovarian cancer cell line models, including the first characterised lines with moderate-high levels of ER. The effects of oestrogen on growth were initially determined in nine ovarian cell lines possessing a range of ER from 0 to 132 fmol/mg protein. Sensitivity to oestrogen correlated with the level of ER expression in that concentrations of 17 β-oestradiol (E2) between 10-12 and 10-6M stimulated the growth of the PEO1, PEO4, and PEO6 cell lines which possess moderate-high levels of receptors between 96 and 132 fmol/mg protein, whereas there was no change in the growth of the PEA1 and PEA2 cell lines which have an ER content of less than 30 fmol/mg protein. The growth of the ER negative lines PEO14, PEO16 and PE023 was also unchanged by E2 treatment. Concentrations of E2 which were stimulatory to the PEO1 cell line were inhibitory to a cisplatin-resistant derivative, PEO1CDDP despite this also possessing moderate-high levels of ER. Effects of E2 on growth were also examined in two ovarian xenograft models grown in nude mice; PEO4 and HOX60 which are ER-positive and ER-negative respectively. Exposure of the xenografts to a subcutaneously planted oestrogen pellet produced a significant inhibition in PEO4 growth but no difference in HOX60 growth as compared to controls. If these results reflect the clinical situation, then there is a valid case for the use of anti-oestrogen therapy in a subset of patients with ovarian tumours expressing moderate-high levels of ER. Agents which interfere with the TGF-α and IGF-mediated growth pathways may also have therapeutic benefit.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available