PARATHYROID HORMONE-RELATED PROTEIN

被引:74
作者
MOSELEY, JM [1 ]
GILLESPIE, MT [1 ]
机构
[1] UNIV MELBOURNE,ST VINCENTS HOSP,DEPT MED,FITZROY,VIC 3065,AUSTRALIA
基金
英国医学研究理事会;
关键词
HUMORAL HYPERCALCEMIA OF MALIGNANCY (HHM); RADIOIMMUNOASSAY; PLACENTA; FETAL DEVELOPMENT; SMOOTH MUSCLE; CYTOKINE;
D O I
10.3109/10408369509084687
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
We review the current state of knowledge of the molecular properties and actions of parathyroid hormone-related protein (PTHrP) both in cancer patients and in normal physiology. PTHrP is a common product of squamous cancers and is the major mediator of the syndrome of humoral hypercalcemia of malignancy (HHM) by its actions through parathyroid hormone receptors in bone and kidney. Recently developed radioimmunoassays and tissue localization techniques indicate that PTHrP is produced by many more cancers than was originally indicated by clinical studies and that it contributes significantly to malignancy-related hypercalcemia associated with other etiologies, for example, cancers metastatic to bone and hematological malignancies. The gene encoding PTHrP is complex, with multiple exons coding for up to 12 alternate transcripts and three different length proteins, potentially in a tissue-specific manner, by the use of three promoters. Its expression is regulated by hormones and growth factors, and the untranslated exons display features in common with many cytokine genes. Although potential endocrine actions of PTHrP are evident in fetal development, further evidence suggesting that the normal physiological role of PTHrP is predominantly as a locally produced regulator/cytokine comes from localization studies and investigations of its actions in a variety of tissues. Such studies indicate that in addition to its parathyroid hormone-like actions, PTHrP has multiple activities, including those in fetal development, placental calcium transfer, lactation, smooth muscle relaxation, and on epithelial cell growth. Although PTHrP was discovered because of its production by cancers, evidence for its actions as a local regulator highlights the importance of understanding its roles not only in the etiology of HHM in cancer patients but also in normal tissues.
引用
收藏
页码:299 / 343
页数:45
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