The Prolactin-Inducible Protein / Gross Cystic Disease Fluid Protein (PIP/GCDFP-15): Genetic Analysis and Hormonal Regulation of Gene Expression

Abstract

The prolactin-inducible protein (PIP)/gross cystic disease fluid protein (GCDFP-15) was isolated by us (1, 2) as a glycoprotein secreted by the T47D human breast cancer cell line in response to lactogenic peptide hormones (human prolactin and human growth hormone) and androgen, and independently by Haagensen and co-workers (3) as a protein found in abundance in the fluid of gross cystic disease of the breast. Haagensen and colleagues (3, 4) have measured the clinical profiles of this protein by radioimmunoassay and immunohistochemistry in the blood and tissues of patients having abnormal breast pathology. Based on immunohistochemical data, these investigators concluded that GCDFP-15 is the product of apocrine glands, and that the production of this protein by gross cystic disease and malignant breast tumors is the result of apocrine differentiation. Beside Haagensen’s group, many clinical laboratories are using the GCDFP-15/PIP as a marker for abnormal breast functions and have observed, for instance, that the contents of GCDFP-15 in gross cystic disease fluid is correlated with that of androgens, prolactin and epidermal growth factor (5). PIP/GCDFP-15 protein is abundant in gross cystic disease and malignant breast carcinomas (2 –4, 6). However, little, if any, of this protein is found in normal human mammary tissue (4). Nevertheless, the protein has been detected by immunocytochemistry in normal apocrine tissues such as the serous cells of the salivary gland, Moll’s glands of eyelids, ceruminous glands of the ear canal, sweat glands, perineum and some bronchial glands (3,4). We have also employed Western immunoblot to demonstrate the presence of PIP/GCDFP-15 protein in a variety of physiological fluids such as blood, saliva, tear, sweat, amniotic fluid and breast milk (7). While the studies on PIP/GCDFP-15 protein distribution and tissue contents are informative, they have provided little insight into the cellular origin (site of synthesis) and functional significance of this protein. Also, the genetic mechanisms governing the expression of the PIP/GCDFP-15 gene (PIP*) in normal and neoplastic tissues remain to be explored. For these reasons, we have directed our research into the molecular genetics of PIP gene. [*Since PIP is the official name used in the Genome Data Base and in both Genbank Data Bank and the EMBL Data base, the GCDFP-15 designation will not be used. Throughout this article, PIP is used to denote the gene.