Rational Design of Competitive Prolactin/Growth Hormone Receptor Antagonists
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- 作者：Estelle Tallet ; Vincent Rouet ; Jean-Baptiste Jomain ; Paul A. Kelly ; Sophie Bernichtein and Vincent Goffin
- 关键词：G120R ; hGH ; G129R ; hPRL ; Δ ; 1– ; 9 ; G129R ; hPRL ; B2036 ; Pegvisomant
- 刊名：Journal of Mammary Gland Biology and Neoplasia
- 出版年：2008
- 出版时间：March, 2008
- 年：2008
- 卷：13
- 期：1
- 页码：105-117
- 全文大小：406.0 KB
- 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Oncology
Cancer Research - 出版者：Springer Netherlands
- ISSN：1573-7039
文摘
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.