Disease relevance of PIP

• Gross cystic disease fluid protein (GCDFP-15), also known as prolactin-inducible protein (PIP), is a specific breast tumor marker [1].
• Mapping the CD4 binding domain of gp17, a glycoprotein secreted from seminal vesicles and breast carcinomas [2].
• Differential antibody reactivity and CD4 binding of the mammary tumor marker protein GCDFP-15 from breast cyst and its counterparts from exocrine epithelia [3].
• The complete amino acid sequence of SABP was determined with the aid of fragments generated by trypsin, Staphylococcus aureus V8 protease and pepsin [4].
• These results suggest that GCDFP-15 and EMA could be the biochemical expression of apocrine metaplasia and epithelial hyperplasia, respectively, two histopathological features which characterize breast cystic disease [5].

Psychiatry related information on PIP

• Furthermore, several proteases were identified in pathological conditions, namely secretases in Alzheimer's disease and gross cystic disease fluid protein 15 kDa in breast cancer, when most likely their physiological substrate is still hidden [6].
• Preoptic area lesions disrupt prolactin-induced parental feeding behavior in ring doves [7].
• Families who had a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar type (SABP) first-degree relative were ascertained for the purpose of identifying genes involved in bipolar affective disorder [8].

High impact information on PIP

• We have purified these activities and found that the principal IL-2-inducible component bears significant relatedness to a prolactin-induced transcription factor first identified in sheep mammary gland tissue [9].
• Increased plasma levels of GCDFP-15 were reflected in increased urinary excretion of the glycoprotein [10].
• Nine (90%) of 10 patients who had 50% increases in plasma GCDFP-15 during initial androgen therapy also had significant decreases in plasma GCDFP-15 following termination of therapy [10].
• Data on 3 prospectively studied patients demonstrated that plasma GCDFP-15 rose within 24 hours of initiation of fluoxymesterone therapy and continued to rise for at least 6 days [10].
• Anandamide suppressed the levels of the long form of the prolactin receptor in both EFM-19 and MCF-7 cells, as well as a typical prolactin-induced response, i.e., the expression of the breast cancer cell susceptibility gene brca1 [11].

Chemical compound and disease context of PIP

• The androgen and prolactin responsive prolactin-inducible protein (PIP)/gross cystic disease fluid protein (GCDFP-15) is expressed in benign and malignant human breast tumors and in such normal exocrine organs as sweat, salivary and lacrimal glands [12].
• In order to better understand the mechanisms responsible for the antagonism between steroids in human breast cancer cells, we have studied the effect of 17 beta-estradiol (E2), dihydrotestosterone (DHT), and dexamethasone (DEX) alone or in combination on the expression of the breast gross cystic disease fluid protein-15 (GCDFP-15) in ZR-75-1 cells [13].
• Cylindromas of the breast and skin did not express cytokeratin 20, gross cystic disease fluid protein 15, or estrogen or progesterone receptor [14].
• Oestradiol-17 beta and tamoxifen regulate the synthesis of a gross cystic disease fluid protein (GCDFP-15) in T47D human breast cancer cells [15].
• Retinoic acid modulates prolactin receptor expression and prolactin-induced STAT-5 activation in breast cancer cells in vitro [16].

Biological context of PIP

• We previously demonstrated that gp17 binds to CD4 with high affinity and strongly inhibits T lymphocyte apoptosis induced by sequential cross-linking of CD4 and T cell receptor (TCR) [2].
• The protein has an amino acid sequence identical to SABP (secretory actin-binding protein), to PIP (prolactin-inducible protein) and to gp17, a protein isolated from human seminal plasma [3].
• A different N-linked glycosylation pattern was observed in pathological GCDFP-15/PIP as compared with physiological gp17/SABP protein by coupling enzymatic digestion and ProteinChip technology [1].
• Prolactin-induced phosphorylation of Stat5 is a key event in the development and differentiation of mammary epithelial cells [17].
• The antiapoptotic effect observed in the presence of gp17 correlates with a moderate up-regulation of Bcl-2 expression in treated cells [18].

Anatomical context of PIP

• The protein is also known under different names in different body fluids such as gp17 in seminal plasma [19].
• gp17, a secretory CD4-binding factor isolated from the human seminal plasma, is identical to the gross cystic disease fluid protein-15, a specific marker for primary and metastatic breast tumors [2].
• The resulting fluorescent protein was inefficiently secreted, thus suggesting that gp17/GCDFP-15 is not appropriately post-translationally processed and/or transported in HeLa cells [20].
• Although SABP was also detected in saliva, in extracts of the submandibular gland and seminal vesicles, little is known of its function [4].
• The highly significant relationship between GCDFP-15 and EGF levels in the medium remains to be elucidated but may be related to an androgen sensitivity in the breast epithelium surrounding the cyst [5].

Associations of PIP with chemical compounds

• Secretory actin-binding protein (SABP), a glycoprotein from human seminal plasma, was isolated according to Akiyama and Kimura [Akiyama, K. & Kimura, H. (1990) Biochim. Biophys. Acta 1040, 206-210] [4].
• The single polypeptide chain of SABP contains 118 amino acids with a calculated Mr of 13,506 and pyroglutamic acid as the N-terminal residue [4].
• We mutated Thr(757) in the C-terminal of Stat5a (Thr-Stat5) to Val (Val-Stat5) and Asp (Asp-Stat5) and examined the effect on nuclear translocation, DNA binding, and prolactin-induced transcriptional activation of a Stat5-responsive luciferase reporter gene [21].
• The inhibitory effect of E2 on GCDFP-15 expression was competitively reversed by the antiestrogen LY156758 [13].
• However, at the concentration used, E2 reversed by only 65% the stimulation achieved by the combination of DHT and DEX on GCDFP-15 mRNA levels [13].

Physical interactions of PIP

• The use of the P. pastoris secretory pathway allowed instead the accumulation in the culture medium of a GCDFP-15/gp17 species which retained the ability to bind to CD4 and also most of the biochemical and immunological properties of the native protein [20].
• Inhibitory effects of anti-prolactin receptor antibodies on prolactin binding in brain and prolactin-induced feeding behavior in ring doves [22].

Regulatory relationships of PIP

• Prostate-specific antigen and gross cystic disease fluid protein-15 are co-expressed in androgen receptor-positive breast tumours [23].
• Interleukin-4 and interleukin-13 inhibit estrogen-induced breast cancer cell proliferation and stimulate GCDFP-15 expression in human breast cancer cells [24].
• Our results show that IL-6 is a potent inhibitory of basal as well as androgen-, glucocorticoid- and IL-1 alpha-induced apo-D and GCDFP-15 secretion in ZR-75-1 human breast cancer cells, while cell proliferation is inhibited by this cytokine [25].
• Exposure to IL-6 markedly decreased dihydrotestosterone (DHT)-induced apo-D and GCDFP-15 release, with a half-maximal effect measured at 13 U/ml [25].
• Role of vasoactive intestinal peptide in the control of prolactin-induced turkey incubation behavior. I. Acute infusion of vasoactive intestinal peptide [26].

Other interactions of PIP

• By comparing the kinetic constants for binding of GCDFP-5 and gp17 to CD4 by biosensor technology, significant differences in binding affinities were observed between the 2 factors, thus reflecting structural differences [3].
• We also show that, among the substrates tested, GCDFP-15/gp17 is specific for fibronectin [19].
• We now report that GCDFP-15/gp17 is a protease exhibiting structural properties relating it to the aspartyl proteinase superfamily [19].
• Expression of WT1, CA 125, and GCDFP-15 as useful markers in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary [27].
• Furthermore, exposure of ZR-75-1 cells of IL-4 and IL-13 increased GCDFP-15 mRNA levels by 5.5- and 6.0-fold, respectively [24].

Analytical, diagnostic and therapeutic context of PIP

• Surface plasmon resonance analysis also showed that anti-GCDFP-15 and anti-gp17 antibodies inhibit the binding of CD4 to GCDFP-15 and gp17, respectively, to different extents [3].
• This protein, namely gp17 (apparent MW = 17,500 Da), was purified by affinity chromatography and characterized by SDS/PAGE analysis [28].
• Immunohistochemistry of a gross cystic disease fluid protein (GCDFP-15) of the breast. A marker of apocrine epithelium and breast carcinomas with apocrine features [29].
• By the immunoperoxidase technique, GCDFP-15 was localized in the apocrine metaplastic epithelium lining breast cysts and in apocrine glands in the axilla, vulva, eyelid, and ear canal [29].
• As a follow up to our previous findings that gp17 binds to CD4 with high affinity and interferes with both HIV-1 gp120 binding to CD4 and syncytium formation, we investigated whether gp17 could affect the T lymphocyte apoptosis induced by a separate ligation of CD4 and TCR [18].

References