In Vitro Regulation of the Progesterone Receptor

Fox, Mark (1994) In Vitro Regulation of the Progesterone Receptor. MSc(R) thesis, University of Glasgow.

Abstract

The single commonest cause of cancer deaths among women is breast cancer, closely followed by lung cancer. As detection methods and treatments improve, the rate of breast cancer deaths will hopefully fall. Surgical removal of all clinically apparent disease is usually the treatment of primary breast cancer, often followed by adjuvant systemic treatments to treat subclinical metastases. There are several appropriate adjuvant systemic treatments, however, the one favoured for hormonally sensitive cancer is endocrine therapy. This treatment is based on the concept that certain tumour cells will retain their sensitivity to hormones (e.g. oestrogen and progesterone). The aim of this type of therapy must therefore be to negate or reverse the proliferative effects of such influential hormones. While it is accepted by clinicians that antiestrogens and progestins provide effective treatment of advanced hormone-sensitive breast cancer, long term usage leads to drug resistance and relapse. A possible approach to overcoming the mechanism of resistance could be to use short bursts of alternative endocrine therapies. Leake et al., (1992) demonstrated that a treatment with Tamoxifen and Megace could give significant advantages when compared to Tamoxifen alone. However, at the end of the progestin component of the cycle there was onset of vaginal bleeding in 13% of patients. One possible solution could be the maintenance of a low level of Norethisterone (10e-9M) through out the cycle. Studies contained within this thesis demonstrated that the Tamoxifen component of the cycle induced PR synthesis in ZR-75-1 cells. The ability of Tamoxifen to maintain PR synthesis was not impaired by the presence of Norethisterone (1x10e-9M). However, higher doses of this progestin did significantly reduce PR levels. Investigations into the effect of Tamoxifen and progestin either alone or together on the proliferation on ZR-75-1 or MCF-7 cells revealed that Tamoxifen induced cell growth. Norethisterone plus Tamoxifen had no effect on either cell line. However, on its own, Norethisterone induced some growth inhibition on MCF-7 cells.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Additional Information: Adviser: Robin Leake
• Keywords: Biochemistry
• Date of Award: 1994
• Depositing User: Enlighten Team
• Unique ID: glathesis:1994-75811
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Dec 2019 09:15
• Last Modified: 19 Dec 2019 09:15
• URI: https://theses.gla.ac.uk/id/eprint/75811