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Notes:
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The mammary gland is the major target tissue of prolactin (PRL) in mammals. Although this
pituitary hormone has been long suspected to be involved in the progression of human breast cancer,
the failure of clinical improvement by treatment with dopamine agonists (which lower circulating
levels of PRL) rapidly reduced the interest of oncologists concerning a potential role of PRL in the
development of breast cancer. Within the last few years, however, several studies reported first, that
PRL is also synthesized by mammary epithelial cells, and second that it may exert a proliferative
action in an autocrine/paracrine manner. In agreement with a recent epidemiological study, these
observations have led to a reconsideration of the role of PRL as an active participant in breast
cancer, and are an impetus to redefine the molecular targets of anti-prolactin strategies since
dopamine analogs are assumed to be inefficient on extrapituitray PRL synthesis. In this review, we
briefly summarize the current knowledge of PRL effects on both normal and tumor mammary cells,
and we discuss the most relevant articles supporting the autocrine-paracrine action of PRL in the
breast. With the aim of defining putative new molecular targets, we propose an overview of the main
PRL receptor signaling cascades known to be triggered by PRL in mammary epithelial cells or,
when not available, in other cell types. Finally, because proteolytic fragments of rat PRL have been
shown to inhibit the angiogenic process, which may be relevant for preventing the progression of
solid tumors such as breast tumors, we discuss the hypothesis that the enzymatic cleavage of human
PRL could also represent a new molecular target in the search for alternative strategies in the
treatment of breast cancer. |
