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The Role of Prolactin in Mammary Carcinoma

Department of Pathology and Laboratory Medicine (C.V.C), University of Pennsylvania, Philadelphia, Pennsylvania 19104; Lombardi Cancer Center (P.A.F.), Department of Oncology, Georgetown University, Washington, D.C. 20057; Channing Laboratories, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, and Department of Epidemiology (S.E.H.), Harvard School of Public Health, Cambridge, Massachusetts 02115; and Department of Comparative Bioscience (L.A.S.), University of Wisconsin, Madison, Wisconsin 53706

Correspondence: Address all correspondence and requests for reprints to: Charles V. Clevenger, M.D., Ph.D., Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104. E-mail: clevengc{at}mail.med.upenn.edu

The contribution of prolactin (PRL) to the pathogenesis and progression of human breast cancer at the cellular, transgenic, and epidemiological levels is increasingly appreciated. Acting at the endocrine and autocrine/paracrine levels, PRL functions to stimulate the growth and motility of human breast cancer cells. The actions of this ligand are mediated by at least six recognized PRL receptor isoforms found on, or secreted by, human breast epithelium. The PRL/PRL receptor complex associates with and activates several signaling networks that are shared with other members of the cytokine receptor superfamily. Coupled with the recently identified intranuclear function of PRL, these networks are integrated into the in vitro and in vivo actions induced by ligand. These findings indicate that antagonists of PRL/PRL receptor interaction or PRL receptor-associated signal transduction may be of considerable utility in the treatment of human breast cancer.

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