The Effect of HMGB1 Protein and Its Truncated Form on the Expression of RAGE Variants in Breast Cancer Cells

Abstract

HMGB1 protein is a DNA binding nuclear protein. Its properties to bind different non-B DNA conformations and also to bend linear DNA implicate the protein in many essential cellular processes as DNA replication, repair, transcription, remodelling, etc. HMGB1 plays important role outside the cell as it is passively released from necrotic cells and actively from apoptotic ones and binds its specific receptor for advanced glycation end products RAGE. HMGB1/RAGE interactin is implicated in various diseases including cancer. Different soluble RAGE forms were reported whose functional role is to serve as a decoy for the ligands and in this way to block the signalling pathway. How the ligands regulate the production of RAGE variants is a subject of great scientific interest. We studied the effect of HMGB1 and its truncated form lacking the C- terminus on the expression of full-length (flRAGE) and soluble RAGE (sRAGE) in breast cancer cell lines: MCF7 represents a hormone dependent cancer with better prognosis and MDA-MB-231 – hormone independent with substantial invasive capacity. HMGB1 stimulates the total RAGE expression in both breast cancer cells but in MCF7 the ratio changes and is in favour of the membrane fraction. The absence of the C-tail of HMGB1 provokes comparable changes in RAGE production in MCF7 cells as the whole HMGB1 molecule. In MDA-MB- 231cell line the total amount of RAGE was slightly affected but it is entirely represented by the membrane form and the soluble one is in negligible amounts.