Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.
RNA interference of endogenous PTHrP caused a significant reduction in cell adhesion of a breast cancer cell line to collagen type I, fibronectin and laminin (P<0.05) and of a colon cancer cell to collagen type I and fibronectin (P<0.05).
We recently identified a unique peptide fragment of parathyroid hormone-related protein (PTHrP), PTHrP(12-48), as a validated serum biomarker in breast cancer patients that correlates with and predicts the presence of bone metastases.
Knocking down PTHrP expression significantly reduced the abilities of the breast cancer cells to inhibit osteoblast differentiation and bone formation in vitro and in vivo.
In this article, we will discuss the current knowledge of the mechanisms underlying PTHrPs actions during normal mammary development and in breast cancer.
PTHrP expression was examined in 177 surgically resected breast carcinoma specimens by immunohistochemistry using a monoclonal antibody against the for PTHrP, The relationship of PTHrP expression with clinicopathological factors was analyzed and the clinical courses of the patients are reported.
In this study we started a more detailed investigation of the possible effects on gene expression arising from the interaction between PTHrP [67-86]-amide and 8701-BC breast cancer cells by a combination of conventional-, differential display-and semi-quantitative multiplex-polymerase chain reaction (PCR) assays.
Together, by controlling the expression of PTHrP and its downstream OPG/RANKL, TF-SB has significant inhibition effects on breast cancer bone metastasis, which indicates a new therapeutic method.
Breast cancer cells produce many known stimulators of bone resorption with significant research effort focused on the role of parathyroid hormone-related protein (PTHrP).
Although the PTHRP-receptor (PTHRP-R) is often coexpressed with PTHRP in PBC, its role in regulating breast cancer cell proliferation and metastases to bone remains unclear.
We have previously reported that high extracellular Ca2+ stimulates parathyroid hormone-related protein (PTHrP) release from human prostate and breast cancer cell lines as well as from H-500 rat Leydig cancer cells, an action mediated by the calcium-sensing receptor (CaR).
DBP-MDA-MB-231-CM reduced osteoblasts to produce osteoprotegerin, an osteoclastogenesis inhibitor, while DBP mediated PTHrP up-regulation, increasing IL-8 secretion in MDA-MB-231 and contributing to breast cancer-mediated osteoclast differentiation and bone resorption.
Two of these seven SNPs are in linkage disequilibrium (LD) with SNPs associated with breast cancer (those near ESR1 and PTHLH), and a third (ZNF365) is near, but not in LD with, a breast cancer SNP.
Paraffin sections of 17 primary and 26 metastatic lesions, 11 of which were in bone, were available for the study: 10 of the 17 (59%) primary lesions, 8 of 11 (73%) breast cancer metastases to bone, and 3 of 15 (20%) metastases to non-bone sites showed specific localization of PTHrP mRNA.
Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer - it influences the initiation and progression of primary tumors and metastases.
These results suggest that transient estrogen- or tamoxifen-induced hypercalcemia in patients with breast carcinoma may be a PTHrP-mediated effect that is a marker of ER positivity.