Prolactin-Inducible Protein: From Breast Cancer Biomarker to Immune Modulator-Novel Insights from Knockout Mice

DNA Cell Biol. 2016 Oct;35(10):537-541. doi: 10.1089/dna.2016.3472. Epub 2016 Sep 7.


The propensity for breast cancers to elicit immune responses in patients is well established. The accumulation of tumor infiltrating lymphocytes within the primary breast tumor has been linked to better prognosis and better response to therapy. The prolactin-inducible protein (PIP) is a 15 kD protein that is expressed under physiological conditions of the breast and is regarded as a marker of mammary differentiation. While highly expressed under pathological conditions of the mammary gland, including breast cancers, PIP is expressed in very few other cancers. Although the function of PIP is not well elucidated, numerous studies suggest that its primary role may be related to host defense and immune modulation. However, evidence to show a direct link between PIP and the immune response has been lacking. In this review, we discuss our recent work with Pip-deficient mice, linking PIP not only to a role in innate immunity but for the first time, providing evidence for a role in cell-mediated immunity. These functional studies in Pip null mice lend new insight into the role of PIP in immunity and suggest that PIP may play a similar immune-regulatory role in breast cancer.

Keywords: CD4+ Th1 cells; IFN-γ; breast cancer; breast cancer biomarkers; immune response; prolactin-inducible protein (PIP).

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • Carrier Proteins / immunology*
  • Glycoproteins / immunology*
  • Humans
  • Membrane Transport Proteins
  • Mice, Knockout
  • Proteins / immunology*
  • Th1 Cells / immunology


  • Carrier Proteins
  • Glycoproteins
  • Membrane Transport Proteins
  • PIP protein, human
  • Proteins
  • SMGP-PIP protein, mouse