The meningioma is a tumour that arises from cells that form a fibrous membrane, covering the brain. They account for around 15percent of intracranial tumours and about 7percent of all people dying from brain tumours. These tumours occur more frequently in women than in men and this has lead to the suggestion that oestrogens have a role in their development and growth. Studies a decade ago with antioestrogens have proved inconclusive and therefore a medical therapy based on anti-endocrine treatment has not been developed. Radiotherapy or surgery is still the only means of treatment. With the latter in mind, we have re-visited the 'endocrine hypothesis' by performing the most extensive screening study so far performed for members of the 'superfamily' of steroid receptors. RNA was extracted from around 140 tumours and RT-PCR was performed. This analysis revealed that the ER, ERalpha, AR, PR, GRalpha, GRbeta, PPARalpha, PPARbeta, PPARgamma was expressed in, 6, 0, 56, 26, 83, 0, 46, 91, and 13percent of the tumour samples, respectively. Our recent studies, have indicated that glucocorticoids reduce apoptotic cell death in response to chemotherapeutic agents. Given that GRs are expressed in so may tumours and the fact that glucocorticoids are given to patients prior to radiotherapy, we have tested whether these steroid hormones modulate cell death. Alone dexamethasone (100nM), reduced metabolic activity by 25percent, as measured by the redox sensitive dye, WST-1. The GR antagonist RU486 (10microM), was able to reverse this effect. Classical apoptosis was observed to be induced in meningioma cultures by the addition of the HMG-CoA enzyme inhibitor, Fluvastatin (10microM). Treatment of meningioma cultures with dexamethasone 24h before exposure to Fluvastatin for 72h, reduced the extent of apoptotic cell death observed. As these experiments with glucocorticoids are preliminary, extrapolation to the treatment scenario is not yet justified.
04 - 06 Apr 2005
British Endocrine Societies