Prolactin-induced protein

Prolactin-inducible protein also known as gross cystic disease fluid protein 15 (GCDFP-15), extra-parotid is_associated_with::glycoprotein (EP-GP), gp17 seminal actin-binding protein (SABP) or BRST2 is a is_associated_with::protein that in humans is encoded by the PIP is_associated_with::gene. It is upregulated by is_associated_with::prolactin and is_associated_with::androgens and downregulated by is_associated_with::estrogen.

Function
The protein has a physiological function in regulation of water transport mainly in apocrine glands in the axilla, vulva, eyelid and ear canal, serous cells of the submandibular salivary gland, serous cells of the submucosal glands of the bronchi, and accessory lacrimal glands as well as cutaneous eccrine glands. It is also found in is_associated_with::amniotic fluid and is_associated_with::seminal fluid. PIP has the ability to bind immunoglobulin G (IgG), IgG-Fc, CD4-T cell receptor suggesting a wide range of immunological functions. PIP also binds to is_associated_with::AZGP1. PIP exerts aspartyl proteinase activity able to cleave is_associated_with::fibronectin.

PIP can bind different species of bacteria showing highest affinity to sterptococci thus playing a role in non-immune defense of the body against pathogenic bacterial strains.

Mitogenic effect of PIP was observed on both normal and malignant breast epithelial cells.

Use as marker and significance in disease
Prolactin induced protein (called GCDFP-15 in this context) in breast cyst fluid or breast tissue serves as marker of both benign and malignant apocrine metaplasia as the protein is not normally expressed in breast tissue. It is characteristic of low grade apocrine carcinoma of the breast, high grade apocrine carcinoma frequently loose expression of this marker. PIP gene expression in breast cancer lines was associated with decreased cell proliferation and invasivenes and an increase of the apoptotic pathway. Many of the genes affected by PIP appear to be regulated by is_associated_with::STAT5.

A mitogenic effect of this protein on experimental breast cells lines MCF10A, MCF7, BT474, MDA-MB231 and T47D was detected. Prolactin-induced protein has also been used for identification and detection of disseminated is_associated_with::breast cancer cells.

The PIP gene is amplified in some breast cancer lines accounting for some of its overexpression, however additional mechanisms are needed to completely explain its overexpression. In T47D breast cancer cells, androgen receptor and is_associated_with::RUNX2 interact to synergistically enhance PIP expression.

In molecular apocrine breast cancer (ER-/AR+) there is a positive feedback loop between is_associated_with::androgen receptor and is_associated_with::extracellular signal-regulated kinase (ERK) via is_associated_with::CREB1 which can be inhibited by anti-androgens. PIP expression is necessary for viability and invasiveness of this subtype of breast cancer.

In ER+ breast cancer, particularly those with very high level of ER expression, PIP appears to play an important role in proliferation and invasion as well as acquired resistance to is_associated_with::tamoxifen.

It has been hypothesized that in is_associated_with::Sjögren's syndrome PIP binds to the C-terminal portion of aquaporin-5 and causes it to be transported to the apical membrane causing disruptions of water transport.