[Molecular biology of parathyroid hormone-related peptide]

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.