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Title: Hormones and growth factors in ovarian cancer cells
Author: Crew, Amanda Jayne
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1992
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Ovarian cancer is the most common cause of death among gynaecological malignancies in women in the UK. Despite this, the mechanisms which control the growth of ovarian cancer are unclear. However, the majority of epithelial ovarian cancers express oestrogen receptors (ER), which suggests that oestrogen may be involved with the growth control. In addition a proportion of ovarian tumours express EGF receptors. The majority also contain TGF-α and a smaller number produce EGF. It is therefore possible that GF and TGF-α are autocrine or paracrine growth regulators in ovarian cancer. Using three serous ovarian adenocarcinoma cell lines, PEO1, PEO4 and PEO14 as model systems, the aim of these studies has been to clarify the role of oestrogen, EGF and TGF-α in ovarian cancer. The PEO1 and PEO4 cell lines express moderate-high levels of oestrogen receptor, whereas the PEO14 cell line is ER-negative. The growth of the ER-positive cell lines was stimulated by the exogenous addition of 17 β-oestradiol, maximally at concentrations between 10-10- and 10-8 M whereas oestrogen produced negligible effects in the ER-ngative cell line, PEO14. Thus, the sensitivity to 17 β-oestradiol correlated with the expression of the ER. The 17β- oestradiol-stimulation of PEO1 and PEO4 cell lines was blocked by incubation with tamoxifen or the 'pure' anti-oestrogen ICI 164,384. Incubation with tamoxifen alone produced growth stimulatory effects at concentrations between 10-12 and 10-8 M in PEO1 and PEO4 cell lines. Similarly incubation with ICI 164,384 produced growth stimulation in these cells, although at concentrations between 10-12 and 10-10 M in the PEO1 cell line and 10-12 and 10-7 M in the PEO4 cell line. Neither anti-oestrogen produced growth stimulatory effects in the ER-negative cell line, PEO14. In all three cell lines, incubation with 17 β-oestradiol, tamoxifen or ICI 164,384 at concentrations greater than 10^-6 M of produced growth inhibitory effects.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available