Steroid receptor analysis is an important means of distinguishing between hormonally responsive and non-responsive mammary cancers; tumors lacking the estrogen and progesterone receptors rarely respond while about 75% of tumors which are positive for both proteins do respond to some form of hormonal manipulation. However, very little is known about the actual mechanism of action of receptors. The goal of the work proposed in this application is to establish whether RNase inhibitor, a regulatory protein present in the cytoplasm of most mammalian cells, in conjunction with the RNase/RNase inhibitor equilibrium, plays a major role in tumor growth dynamics, and might be a useful marker of hormone action in breast cancer. Experiments are designed using the transplantable rat mammary tumor MTW9; tumors in the growing, regressing or benign state will be analyzed for RNase, RNase inhibitor, and steroid receptors, to determine how these activities relate to tumor development. The methodology will involve analyses on both acid and alkaline RNase activities, in cytosol and lysosomal fractions, and determination of RNase inhibitor by radioimmunoassay (in addition to RNase binding ability). Purification of RNase activities will be attempted using affinity chromatography as well as conventional techniques.
| Feldman, M; Kohtz, D S; Kleinberg, D L (1988) Isolation and characterization of monoclonal antibodies against ribonuclease inhibitor. Biochem Biophys Res Commun 157:286-94 |
