Ikeda K
Health Care Center, University of Tokyo.
Nihon Rinsho. 1995 Apr;53(4):835-43.
Parathyroid hormone-related peptide (PTHRP) was identified as a major "humor" responsible for humoral hypercalcemia of malignancy (HHM) syndrome. Human PTHRP gene, located on the short arm of chromosome 12, is thought to belong to the same gene family as PTH gene on chromosome 11. Unlike PTH, PTHRP is a product of almost all normal tissues, both fetal and adult, and plays diverse physiologic roles in a paracrine/autocrine fashion. These include 1) regulation of cellular proliferation and differentiation, 2) development of fetus, especially cartilage and bone system, 3) relaxation of vascular and non-vascular smooth muscle, and 4) maintenance of reproduction system. The expression of PTHRP gene in normal tissues is tightly regulated by a number of factors, involving both transcriptional and post-transcriptional mechanisms. PTHRP overproduced and secreted by certain malignancies enters the circulation, interacts with a common receptor for PTHRP and PTH, and causes hypercalcemia in cancer patients. Although the molecular and cellular mechanism by which PTHRP gene is constitutively activated in association with cellular transformation remains to be elucidated, accumulating evidence suggests complex mechanisms involving oncogene products, growth factors and various transcription factors.
甲状旁腺激素相关肽（PTHRP）被确定为导致恶性肿瘤体液性高钙血症（HHM）综合征的主要“体液因子”。人PTHRP基因位于12号染色体短臂，被认为与11号染色体上的PTH基因属于同一基因家族。与PTH不同，PTHRP是几乎所有正常组织（包括胎儿和成人组织）的产物，并以旁分泌/自分泌方式发挥多种生理作用。这些作用包括：1）调节细胞增殖和分化；2）胎儿发育，尤其是软骨和骨骼系统的发育；3）血管和非血管平滑肌的舒张；4）维持生殖系统。PTHRP基因在正常组织中的表达受到多种因素的严格调控，涉及转录和转录后机制。某些恶性肿瘤过度产生和分泌的PTHRP进入循环系统，与PTHRP和PTH的共同受体相互作用，导致癌症患者出现高钙血症。尽管PTHRP基因在细胞转化过程中被组成性激活的分子和细胞机制仍有待阐明，但越来越多的证据表明这涉及癌基因产物、生长因子和各种转录因子的复杂机制。
