Histochemical detection of steroid hormone receptors and steroid action in human tumour cell lines

Receptor levels as such will probably never give a 100% accurate prediction about the sensitivity of tumours to hormones, due to the limitations of obtaining truely representative samples of tumour tissues as well as the inherent limitations of the receptor being only one of the parameters involved in steroid hormone action. Both mammary and prostate carcinoma are histopathologically heterogeneous tissues and because most biochemical receptor assays are performed on tissue homogenates, it is difficult to predict responses on the basis of a single biopsy. To allow for a more precise, cell by cell analysis of the receptor content in a heterogeneous tumour specimen, histochemical methods have been developed. With such histochemical methods it might be possible to determine which or how many cells actually contain receptors and these methods might offer also a possibility for detection of receptors in small amounts of tissue or needle aspirations. One of the aims of the studies presented in this thesis was to investigate whether histochemical methods (cytofluorescence, autoradiography and immunocytochemistry) can be used for a reliable determination of steroid hormone receptors (Chapters 4, 5 and 6). It is well known that the binding of the hormone to the receptor is only the first step in a complex pathtvay leading to the physiological effects of hormones. Hence to obtain a proper parameter for hormone actions it would be more meaningful to develop assays that directly measure the responsiveness of tumours with respect to grmowth rather than simply the presence of receptors. In this regard the second aim of our studies was to investigate the effects of steroids on the proliferation of tumour cells in vitro, since steroids may influence cell proliferation and specific protein secretion (Chapter 7).