Prolactin and murine mammary tumorigenesis: a review.

TLDR

Prolactin is a key hormone in murine mammary tumorigenesis, acting in both initiation and promotion phases of the Berenblum two‑step model by modulating epithelial metabolism and influencing whether transformed cells proliferate or differentiate. The study aims to determine whether prolactin significantly influences human breast tumorigenesis and, if so, whether its suppression could provide prophylactic or chemotherapeutic benefit. Prolactin can directly or indirectly stimulate mitotic activity of transformed mammary epithelium during promotion, or, in the presence of hormones such as glucocorticoids, synergistically induce differentiation during antipromotion. Tumor development occurs when prolactin promotes transformed epithelium, but not when it induces differentiation.

Abstract

It is unequivocal that prolactin is an influential hormone in murine mammary tumorigenesis. The Berenblum hypothesis (7), a well-known theoretical model of tumorigenesis that depicts this oncogenic process as a two-step mechanism, i.e., initiation and promotion, is a conceptual scheme in which the action of prolactin in mammary tumorigenesis may be understood. According to this conceptual model, prolactin would participate in both the initiation and promotion steps of mammary tumorigenesis, In the initiation phase, variations in prolactin secretion appear to influence the metabolism of the mammary epithelium, so that the epithelium would be either more receptive to or refractory to an initiating agent (e.g., chemical carcinogen, physical carcinogens, oncogenic viruses, ets.) i.e., a permissive action. In the promotion phase, prolactin may act as either a promoter or an antipromoter of the "transformed" mammary epithelium. In promotion, the hormone may either directly or indirectly (via the ovary) stimulate mitotic activity of the "transformed" epithelium. In antipromotion the hormone, in the presence of requisite hormones (e.g., glucocorticoids), may synergistically induce differentiation (e.g., lactation) in the "transformed" epithelium. A tumor would result in the former (promotion) but not in the latter (antipromotion) case. Whether or not prolactin is significantly influential in human breast tumorigenesis remains to be determined. This is an extremely important area of research which is justifiably receiving increased attention. For if prolactin can be shown to influence human breast epithelium in a manner similar to its effect on rodent mammary tissue, then prophylactic and/of chemotherapeutic control of human breast tumorigenesis may be feasible by appropriate drug-mediated prolactin suppression.