The oncogenic potential of autocrine human growth hormone in breast cancer
- Institute for Molecular Biosciences, University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
Given the mortality associated with metastatic breast cancer, the identity and role of factors promoting this process are of major health significance, and the study by Mukhina et al. (1) in this issue of PNAS provides such a factor. The important role of estrogens in breast cancer is exemplified by the clinical value of antiestrogens and aromatase inhibitors and by the utility of estrogen receptor status in determining patient prognosis. Increased Her2/Neu expression in estrogen receptornegative patients is an indicator of poor prognosis associated with metastasis, and it has resulted in the development of a clinically useful monoclonal antibody directed to the extracellular domain of HER2, Trastuzumab (Herceptin). HER2 status also provides a useful indicator of the response of breast cancer to other therapies such as topoisomerase inhibitors and anthracyclines. The paralog of the HER2 ligand, heregulin, epidermal growth factor, is an important mammary gland developmental factor, as is estrogen. One might therefore predict that other key hormones and growth factors regulating mammary gland development would be candidate promoters for breast cancer. For example, growth hormone (GH) has important roles in ductal elongation and the differentiation of ductal epithelia into terminal end buds, whereas prolactin is necessary for normal lobular epithelial cell proliferation and secretory function. Attention has focused on prolactin as a potential breast tumor promoter because it was early shown to act in this way with rat mammary carcinomas (2), and overexpression of prolactin in mammary tissue induces tumors in mice (3). The situation in human breast cancer is not so clear, because both prolactin and GH are able to activate the prolactin receptor in humans, and the homologous GH and prolactin receptors activate very similar signaling pathways. These class 1 cytokine receptors activate not only the Janus kinase 2 and signal transducers and activators of …
