Prolactin and growth hormone in breast cancer. Studies of human breast cancer and transgenic tumor models

Abstract

Prolactin (PRL) and growth hormone (GH) are two related pituitary peptide hormones of importance during normal mammary gland development. Furthermore, their involvement in development and growth of malignant mammary tumors has been suggested by several investigators. By producing rat PRL transgenic (rPRL) mice and bovine GH transgenic (bGH) mice it was shown that activation of the PRL receptor (PRLR) but not the GH receptor (GHR) is important for mammary tumor development in mice. Mammary explant organ culture studies suggest a functional role of rPRL locally produced in the mammary gland.Studies of rPRL mammary glands with different degrees of hyperplasia showed that the percentage of estrogen receptor a (ERa)-expressing epithelial cells was markedly increased in severely hyperplastic rPRL mammary glands. Plasma levels of 17ß-estradiol, estimated over a 34-day period of time were increased in rPRL mice, while progesterone levels were unchanged compared to control animals. Together these data suggest a role of increased ERa activation during mammary tumor development in rPRL mice. It was also shown that insulin-like growth factor (IGF)-I receptor (IGF-IR) activation is important for rPRL mammary tumor cell growth in vitro, while mRNA expression levels of IGF-I, IGF-II and IGF-IR in rPRL mammary glands do not increase during the course of mammary tumor development.GHR expression was studied in human breast cancer specimens, and it was found that nearly all tumors analyzed expressed GHR. By immunohistochemical studies and by western blot analyses it was found that GHR expression was increased in most tumor tissues compared to adjacent normal mammary tissues.