mRNA species directing synthesis of milk proteins in normal and tumour tissue from human mammary gland

Abstract

ONLY about one third of human metastatic breast carcinomas regress in response to hormone therapy^1,2, so there is a need to predict which tumours are of the hormone-dependent type. The usual method of prediction is based on the determination of hormone receptors in the tumour tissue^2–5. However, only about one half of the tumours containing measurable oestrogen-receptor levels respond to hormone treatment² suggesting that receptors which bind the hormone in vitro may not always respond in vivo. An alternative approach has been to look for milk proteins within the tumour or serum, as lactation is a known hormone-dependent process. Although the rationale behind this approach has been substantiated in experimental systems^6,7 results with human mammary carcinomas are inconclusive^8–16, probably because of insufficient specificity¹⁷ and sensitivity of the radioimmunological protein assay on which this method depends. In addition to technical problems the immunological approach has the drawback that it can only monitor the final product of hormone action, the mature protein, and not the initial RNA transcript(s). A better approach would seem to be an assay designed to detect differences in transcriptional rather than translational activity. As a preliminary step towards this objective, we describe here the isolation of poly(A)-containing RNA from a normal lactating human mammary gland, and demonstrate the presence of mRNA species which direct the synthesis in cell-free protein-synthesising systems of human casein and α-lactalbumin. Moreover, using the same techniques we have identified the presence of mRNA directing the synthesis of ^α-lactalbumin in poly (A)-containing RNA isolated from two out of five mammary tumours examined.