Pathogenesis of Paget disease of the breast as a consequence of the motility factor heregulin-α

Heregulin-α messenger RNA is produced by the nipple epidermal keratinocytes, which secrete heregulin-α protein. Heregulin-α then binds to a heterodimer of HER3 and HER-2/NEU or of HER4 and HER2/NEU on Paget cells. HER1 is expressed on the membranes of some normal epidermal cells and does not appear to be involved in the pathogenesis of Paget disease.