The regulation of RANK and RANKL mRNA expression through activation of the JAK2/STAT5a pathway in human breast cancer cell lines ©

Abstract

The receptor activator of nuclear factor-kB (RANK) and its ligand, RANKL has have been implicated as an important link between breast cancer and metastasis to bone because of their ability to activate intracellular signal cascades leading to altered cancer cell behaviour and bone breakdown. The JAK/STAT5a cell signaling pathway is also crucial to breast biology and is involved in transcriptional regulation of many genes. The objective of this study is to determine if RANKL mRNA expression is regulated through the JAK/STAT5a pathway by stimulating human breast cancer cell lines, MCF-7 and MDA-MB-231, with prolactin (PRL), epidermal growth factor (EGF) and heregulin-beta1 (HRG-1), all known to activate STAT5a and play a role in breast cancer progression. This study shows that RANKL expression is upregulated by PRL, EGF and HRG-1, and that PRL and HRG-1 regulate transcription through the JAK/STAT5a pathway.