Prolactin: The Forgotten Hormone of Human Breast Cancer
Introduction
One of the most intriguing questions in mammary gland biology is why prolactin (PRL), which clearly is involved in normal breast development in rodents and humans and clearly plays a role in rodent mammary cancer Welsch and Nagasawa 1977, Vonderhaar and Biswas 1987, has not been accepted as a player in human breast cancer. For any hormone, such as estrogen, to be accepted as playing a role in breast cancer, three criteria are applied. First, there must be specific receptors for the hormone on the cancer cells. Second, the hormone must induce a biological response. Third, the course of the disease must be altered when the action of the hormone is specifically inhibited at the target (as is the case with antiestrogens and estrogen effects) or the source of the hormone is removed, i.e., through ovariectomy. When these same criteria are applied to PRL, a role for this hormone in breast cancer can be argued.
Section snippets
Receptor Forms
The presence of specific receptors for PRL has been demonstrated in both normal and malignant mammary glands. PRL receptors belong to the cytokine hematopoietic family of receptors (Kelly et al., 1991). The members of this superfamily are single membrane-spanning receptors organized into three domains comprising an extracellular ligand-binding domain, a hydrophobic transmembrane domain, and an intracellular domain containing a proline-rich motif. The three different forms of the PRL receptor
Prolactin as Mitogen in Vivo
In the mammary gland, PRL is both a differentiating agent and a mitogen. It is the mitogenic action that is important in breast cancer. In the normal gland, PRL’s most fundamental actions are at the level of growth and maintenance of the morphology of the mammary gland. Although the ovarian steroids, estrogen and progesterone, are involved in the ductal growth and branching, lobulo-alveolar development and extensive growth of the alveolar cells in the rodent require PRL Vonderhaar 1984,
Serum Prolactin Levels in Breast Cancer Patients
Historically, the third criterion has been the most difficult to satisfy in terms of PRL’s action in human breast cancer. From 60 to 85% of human breast cancer biopsies contain immunologically detectable PRL Purnell et al. 1982, Agarwal et al. 1989, whereas specific PRL receptors have been demonstrated in over 70% of the biopsy samples Codegone et al. 1981, Peyrat et al. 1981, Bonneterre et al. 1982, L’Hermite-Baleriaux et al. 1984. However, there is no clear correlation between circulating PRL
Conclusion
The demonstration of synthesis of PRL by human breast cancer cells suggests that manipulation of pituitary PRL is not a valid approach to therapy for this disease and that new approaches based on the concept of an autocrine/paracrine PRL may be necessary. These observations suggest that the use of specific drugs acting as antilactogens (Das et al., 1994) or analogues of the hormone that antagonizes PRL action at the target tissue Dattani et al. 1995, Fuh and Wells 1995, Goffin et al. 1996, Mode
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2017, Pharmacology and TherapeuticsCitation Excerpt :Paradigmatic observations and recently published data are discussed below. For further information and references to other original studies, the readers are invited to refer to the many reviews that have been published in the field (Arendt & Schuler, 2008; Clevenger et al., 2003, 2009; Fernandez, Touraine, & Goffin, 2010; Goffin & Touraine, 2015; Idelman, Jacobson, Tuttle, & Ben Jonathan, 2011; Lapensee & Ben Jonathan, 2010; O'Leary, Shea, & Schuler, 2015; Shemanko, 2016; Vonderhaar, 1998; Wagner & Rui, 2008). Animal studies involving genetically-induced mammary tumorigenesis (i.e. endogenous tumors) unanimously agree on the pro-tumorigenic role of PRLR signaling in vivo.
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2010, Trends in Endocrinology and MetabolismCitation Excerpt :That the skin produces PRL is not surprising, considering one of the defining features of mammals, the mammary gland, is an epidermal derivative developmentally related to sweat glands [6], whose epithelium is an important extrapituitary site of PRL expression [6]. The major regulatory role of PRL in mammary gland development, growth and function [7] and its potential role in mammary tumorigenesis [8], have long raised questions about its role in skin biology and pathology [9], including whether PRL might also regulate the second defining skin feature of mammals, the hair follicle (HF). PRL, whose gene is located on chromosome 6 in humans [10], is primarily produced under inhibitory dopaminergic control in the anterior pituitary gland [11].
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2009, Molecular and Cellular EndocrinologyEstrogen stimulates transcription from the human prolactin distal promoter through AP1 and estrogen responsive elements in T47D human breast cancer cells
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