Methylation of specific CpG sites in the P2 promoter of parathyroid hormone-related protein determines the invasive potential of breast cancer cell lines.

Parathyroid hormone-related protein (PTHrP) is upregulated in primary breast cancers and a major candidate for osteoclastic bone resorption present at sites of breast cancer to bone metastases. Using a human model of mammary epithelial cell lines differing in tumorigenicity and PTHrP expression, we investigated the role of epigenetic modifications for PTHrP expression. Quantitative analysis of the DNA methylation patterns at a total of 104 CpGs in the promoter region of PTHrP by pyrosequencing showed the absence of methylation in all analyzed cell lines in the large CpG island upstream of exon 1C.

8Cl-cAMP modifies the balance between PKAR1 and PKAR2 and modulates the cell cycle, growth and apoptosis in human adrenocortical H295R cells.

Various types of protein kinase A (PKA) alterations have been observed in adrenocortical tumours and Carney complex (CNC). PKA is a heterotetramer of two regulatory and two catalytic subunits. The R1A and R2B proteins are the most abundant regulatory subunits in endocrine tissues.

Differential expression of parathyroid hormone-related protein in adrenocortical tumors: autocrine/paracrine effects on the growth and signaling pathways in H295R cells.

Adrenocortical tumors (ACT) are rare and heterogeneous, but their pathogenesis is unclear. The oncoprotein parathyroid hormone-related protein (PTHrP), found in many common tumors, can regulate their growth in an autocrine/paracrine fashion through the PTH-R1 receptor. Little is known about the role of PTHrP in ACT.

Amphiregulin-EGFR signaling regulates PTHrP gene expression in breast cancer cells.

Parathyroid hormone-related protein (PTHrP) is an autocrine/paracrine factor produced by breast cancer cells that is speculated to play a major role in permitting breast cancer cells to grow into the bone microenvironment by stimulating the bone resorption axis. It has been previously shown that EGFR signaling induces the production of PTHrP in several primary and transformed epithelial cell types. Therefore, we investigated the relationship between EGFR and PTHrP gene expression in human breast cancer cells.

PTHrP P3 promoter activity in breast cancer cell lines: role of Ets1 and CBP (CREB binding protein).

Parathyroid hormone-related protein (PTHrP) is produced by many tumors including breast cancer. We have reported that Ets1 factor activates P3 PTHrP promoter in our model of tumorigenic breast cancer cell and not in pre- or non-tumorigenic cell lines, thus contributing to an increased PTHrP production. In this study, gel retardation assays revealed that Etsl and its promoter binding site (EBS) specifically formed complexes whose abundance correlates with Ets1 levels in the three cell lines.