Mid‐region parathyroid hormone‐related protein is a genome‐wide chromatin‐binding factor that promotes growth and differentiation of HB2 epithelial cells from the human breast

: Human parathyroid hormone-related protein (PTHrP) is a polyhormone that undergoes proteolytic cleavage producing smaller peptides which exert diversified biological effects. PTHrP signalization is prominently involved in breast development and physiology, but the studies have been focused onto either N-terminal species or full-length protein introduced by gene transfer techniques. Our present work investigates for the first time the effect of the mid-region PTHrP secretory form, that is, the fragment [38-94], on HB2 non-tumoral breast epithelial cells. We examined viability/proliferation of cells grown in PTHrP-containing media supplemented with different serum concentration and on different substrates, extending our investigation to check whether (a) by analogy with MDA-MB231 cells, also HB2 cell chromatin possesses genome-wide binding sites for mid-region PTHrP, and (b) the peptide is endowed with modulating properties toward the expression of proliferation/differentiation signatures by HB2 cells. Our results indicate that mid-region PTHrP acts as a cell growth/differentiation stimulator in routine and "nutrient stress" culture conditions, accordingly reprogramming gene expression, and is able to bind to cytogenetic preparations from HB2 cells. This supports the concept that the physiological mechanisms involving PTHrP during breast development may include mature processed forms of the protein different from the N-terminal fragment. © 2018 BioFactors, 45(2):279-288, 2019.