TISSUE-SPECIFIC ANDROGEN-INHIBITED GENE-EXPRESSION OF A SUBMAXILLARY-GLAND PROTEIN, A RODENT HOMOLOG OF THE HUMAN PROLACTIN-INDUCIBLE PROTEIN GCDFP-15 GENE

The human PRL-inducible protein (PIP)/gross cystic disease fluid prote in-15 is expressed in pathological conditions of the mammary gland and in several exocrine tissues, such as the lacrimal, salivary, and swea t glands. In human breast cancer cells, the expression of PIP/gross cy stic disease fluid protein-15 is stimulated by androgen and PRL, and i nhibited by estrogen. However, it is not known whether the expression of PIP in other tissues is under similar hormonal regulation. In the p resent study we employed reverse transcriptase-polymerase chain reacti on followed by rapid amplification of complementary DNA (cDNA) ends to amplify the PIP cDNA homolog, the submaxillary gland protein (SMGP) i n the mouse. The mouse PIP/SMGP cDNA encodes a putative secreted pepti de of 144 amino acids with a 51% identity with human PIP. Using the mo use PIP/SMGP cDNA as a probe, we examined the tissue- and cell-specifi c expression of PIP/SMGP messenger RNA by in situ hybridization and No rthern blot analysis of mouse and rat tissues. Hormonal regulation was also studied in the rat. PIP/SMGP messenger RNA expression was only d etected in the lacrimal and submaxillary glands of the rodents. In the rat submaxillary gland, PIP/SMGP gene expression was confined to the acinar cells. In the male rat lacrimal gland, castration resulted in a n increase in expression, and in both male and female rats, androgen r eplacement abolished PIP/SMGP gene expression. This pattern of regulat ion was not observed in the submaxillary gland and was actually revers ed in human breast cancer cells. PRL had no effect on the regulation o f PIP/SMGP in either salivary or lacrimal glands. Our study indicates that tissue-specific factors are important in determining the hormone responsiveness of the PIP/SMGP gene. Regulation of the PIP/SMGP gene i n vivo may provide a useful model system to study the mechanism of dow n-regulation of expression by androgen in a tissue-specific manner.