The mammary gland.

In vivo studies have shown that the growth of the mammary gland is regulated by a complex synergistic interaction of protein, steroid and thyroid hormones, but it has proved difficult to fully reproduce these effects in vitro. It is becoming apparent that the hormones classically recognized as involved in mammary growth (oestrogen, progesterone, prolactin, GH, adrenal corticoids, triiodothyronine) bring about effects on epithelial cell proliferation at least in part through growth factors produced at distant sites (such as the liver) and also locally by mammary tissue, both parenchyma and stroma. Growth factor receptors can be demonstrated in mammary tissue. Receptor occupancy generates intracellular signals which enable cells to progress through the cell cycle, leading in ways still not understood to DNA synthesis and cell division. Within the mammary gland there probably exists a balance of stimulatory factors (such as IGFs and EGF/TGF-alpha) and inhibitory factors (such as TGF-beta). Interactions between epithelial and stromal cells, involving growth factors and the extracellular matrix, bring about pattern formation. Growth factors may also play some part in mammary differentiation and function, although the evidence here is less clear. Growth factors are also implemented in the failure of growth regulation which neoplastic transformation represents. Breast cancer cells can synthesize and secrete a variety of growth factors which may stimulate tumour growth through local autocrine/paracrine mechanisms. The oestrogen dependence of some breast cancers may involve oestrogen regulation of and interaction with growth factors, progression to hormone independence involving loss of this control. It is significant that the proteins which protooncogenes encode include growth factors and growth factor receptors. Much remains to be learnt about the nature and control of growth factors produced by and acting on the mammary gland. In breast cancer, this research offers the possibility of new methods of diagnosis and treatment.