Uteroglobin

Abstract: In this report, we describe a novel cDNA isolated from a primary human breast adenocarcinoma and differentially expressed in several breast carcinoma cell lines. The protein encoded by this cDNA, which we have named mammaglobin, is homologous to a family of secreted proteins that includes rat prostatic steroid-binding protein subunit C3, human Clara cell 10-kilodalton protein, and rabbit uteroglobin. Expression of the mammaglobin gene is restricted to the adult mammary gland. More significantly, in an analysis of 35 breast tumor biopsies, mammaglobin mRNA levels were increased at least 10-fold relative to normal breast tissue in 23% of cases. The breast-specific expression of this potentially secreted protein and its frequent overexpression in primary human breast tumors suggest that mammaglobin may be a novel marker for the management of breast cancer.

Abstract: UG or blastokinin is a low molecular weight protein which is secreted by the endometrium of the rabbit during early pregnancy. Its synthesis and secretion by the endometrium are regulated by ovarian steroids, especially P. However, the protein is also produced by tracheo-bronchial, gastrointestinal, prostatic, and seminal vesicular epithelium. In the respiratory tract, UG synthesis is under glucocorticoid control. The hormonal regulation of UG synthesis in organs other than the endometrium and tracheobronchial epithelium is poorly understood. The structure of this protein and its gene has been extensively investigated while its physiological function is still unclear. Since UG, after reduction of its two disulfide bonds, has the ability to bind P and related steroids, it has been suggested that this protein is a P carrier or a P scavenger. However, the protein does not bind glucocorticoids, estrogens, or androgens and its presence in organs other than the uterus cannot be explained on the basis of its P binding. Recent data indicate that UG has other interesting biological properties. These include antichemotactic/antiphagocytic effects on macrophages, monocytes, and neutrophils, tolerogenic effect on both blastomeres and spermatozoa against recognition by maternal lymphocytes, and its ability to inhibit thrombin-induced platelet aggregation. Moreover, UG has been shown to be a potent phospholipase A2 inhibitor. The latter property could suggest a possible mechanism of some of the observed biological effects of this protein. The structural similarities of UG with phospholipase A2 and with other PLA2 inhibitory proteins like lipocortins may suggest that the physiological function of this protein may be primarily immunomodulatory through its function as a PLA2 inhibitor. The possible occurrence of similar proteins in other species, including humans, may confirm this hypothesis. Additionally, our hypothesis may lend support to the suggestion that P may be nature's immunosuppressant during pregnancy.