Rational Design of Competitive Prolactin/Growth Hormone Receptor Antagonists |
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Authors: | Estelle Tallet Vincent Rouet Jean-Baptiste Jomain Paul A Kelly Sophie Bernichtein Vincent Goffin |
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Institution: | (1) Inserm, U845, Centre de Recherche “Croissance et signalisation”, Equipe “PRL, GH et tumeurs”, Paris, 75015, France;(2) Faculté de Médecine, Université Paris Descartes, Paris, 75015, France;(3) Faculté de Médecine Necker, INSERM U845, 156 rue de Vaugirard,, Paris, 75015, France |
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Abstract: | There is increasing evidence that prolactin (PRL) and growth hormone (GH) act as growth-promoters of breast tumors. Recent
arguments have accumulated to suggest that when they are locally-produced within the mammary tissue, these hormones, acting
by an autocrine-paracrine mechanism may have enhanced, or even specific functions compared to endocrine PRL and GH. Classical
drugs blocking pituitary hormone production (dopamine and somatostatin analogs) are ineffective on extrapituitary expression
of PRL/GH genes, therefore the undesirable effects of these locally-produced hormones remain a target of interest for alternative
strategies. This has encouraged the development of competitive PRL and/or GH receptor antagonists, which involve engineered
variants of natural receptor ligands (PRL or GH) aimed at blocking receptor activation rather than hormone production in peripheral
tissues. This article overviews the rational design of this new class of molecules, their specific molecular features (receptor
specificity, biological properties, etc.) and whenever available, the data that have been obtained in cell or animal models
of breast cancer. |
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Keywords: | G120R-hGH G129R-hPRL Δ 1– 9-G129R-hPRL B2036 Pegvisomant |
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