Prolactin-induced protein in breast cancer.

Abstract

Prolactin-induced protein (PIP) is a 17-kDa single polypeptide chain that is secreted by a number of normal apocrine cells, such as milk, saliva, and seminal fluid. PIP is widely expressed in breast cancer and is commonly used as a diagnostic biomarker for the histopathological diagnosis of this disease. Expression of PIP in breast cancer is regulated by androgen and prolactin through a number of transcription factors and signaling cross-talks, including STAT5, Runx2, and CREB1. Notably, PIP is induced by a positive feedback loop between androgen receptor (AR) and extracellular signal-regulated kinase (ERK). The available data indicate that PIP has an aspartyl protease activity that can degrade fibronectin. Importantly, PIP is necessary for outside-in activation of integrin-β1 signaling pathway and regulation of key downstream signaling targets of this pathway such as interaction of integrin-β1 with integrin-linked kinase 1 (ILK1) and ErbB2. Furthermore, the importance of PIP in cell proliferation has been demonstrated by the fact that purified PIP promotes growth of breast cancer cells and PIP expression is necessary for the proliferation of T-47D and MDA-MB-453 cell lines. In addition to cell proliferation, PIP mediates invasion of breast cancer cells in a process that partially depends on the degradation of fibronectin by this protein. Therefore, PIP is a breast cancer-related protein that is expressed in a majority of breast tumors and has a significant function in the biology of this disease.