Multiple actions of parathyroid hormone‐related protein in breast cancer bone metastasis
Abstract
The sequence similarity within the amino‐terminal regions of parathyroid hormone (PTH) and PTH‐related protein (PTHrP) allows the two to share actions at a common site, the PTH1 receptor. A number of biological activities have been ascribed to actions of other domains within PTHrP. PTHrP production by late stage breast cancer has been shown to contribute to bone metastasis formation through promotion of osteoclast formation and bone resorption by action through PTH1 receptors. There is evidence also for a role for PTHrP early in breast cancer that is protective against tumour progression. No signalling pathway has been identified for this effect. PTHrP has also been identified as a factor promoting the emergence of breast cancer cells from dormancy in bone. In that case, PTHrP does not function through activation of PTH1 receptors, despite having very substantial effects on transcriptional activity of the breast cancer cells. This indicates actions of PTHrP that are non‐canonical, that is, mediated through domains other than the amino‐terminal. It is concluded that PTHrP has several distinct paracrine, autocrine, and intracrine actions in the course of breast cancer pathophysiology. Some are mediated through action at PTH1 receptors and others are controlled by other domains within PTHrP.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 02, 2019
- Source ID
- 10.1111/bph.14709
Entities
People
- Rachelle W. Johnson
- T John Martin
Organizations
- Defense Health Agency
- National Health and Medical Research Council
- National Institutes of Health Clinical Center
- University of Melbourne
- Vanderbilt University