Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11684 (Uteroglobin)
 114 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phospholipase A2 (PLA2) is a key enzyme that initiates the arachidonic acid cascade responsible for the synthesis of prostaglandins and leukotrienes, compounds well known for their inflammatory properties. Inhibition of this enzyme may modulate prostaglandin and leukotriene tissue levels. Uteroglobin is a potent PLA2 inhibitor found in rabbit uterus, prostate, seminal vesicle, and tracheobronchial tree. Tissue from ten human patients undergoing prostatectomy was examined for presence of a uteroglobin-like protein. Seven patients underwent transurethral resection and three had an open prostatectomy. Preoperative diagnosis in nine of the 10 patients was benign prostatic hypertrophy. One suspected, poorly differentiated, adenocarcinoma was confirmed and one unsuspected, well differentiated, adenocarcinoma was discovered. Specimens were submitted for Western blot, electron microscopy with immunogold staining, radioimmunoassay, and immunofluorescence. Six patients had evidence of uteroglobin-like protein, three with high levels (greater than or equal to 1000 pg./mg. protein), two with moderate levels (75 to 250 pg.), one with a low level (less than or equal to 75 pg.). Uteroglobin-like protein was present in all three patients who underwent open prostatectomy and in three of the seven patients with transurethral resections. The uteroglobin-like protein level was 2.5 to five times greater in both prostatic utricle specimens. All four assays corroborated these results. Because rabbit uteroglobin coats sperm and masks spermatic antigenicity in the rabbit female genital tract, this report of biochemical and immunological evidence for uteroglobin-like protein in the human prostate may have implications for human male fertility.
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PMID:Expression of a uteroglobin-like protein in human prostate. 245 29

Uteroglobin (UG) is a multifunctional, secreted protein that has receptor-mediated functions. The human UG (hUG) gene is mapped to chromosome 11q12.2-13.1, a region frequently rearranged or deleted in many cancers. Although high levels of hUG expression are characteristic of the mucosal epithelia of many organs, hUG expression is either drastically reduced or totally absent in adenocarcinomas and in viral-transformed epithelial cells derived from the same organs. In agreement with these findings, in an ongoing study to evaluate the effects of aging on UG-knockout mice, 16/16 animals developed malignant tumors, whereas the wild-type littermates (n = 25) remained apparently healthy even after 11/2 years. In the present investigation, we sought to determine the effects of induced-expression of hUG in human cancer cells by transfecting several cell lines derived from adenocarcinomas of various organs with an hUG-cDNA construct. We demonstrate that induced hUG expression reverses at least two of the most important characteristics of the transformed phenotype (i.e., anchorage-independent growth on soft agar and extracellular matrix invasion) of only those cancer cells that also express the hUG receptor. Similarly, treatment of the nontransfected, receptor-positive adenocarcinoma cells with purified recombinant hUG yielded identical results. Taken together, these data define receptor-mediated, autocrine and paracrine pathways through which hUG reverses the transformed phenotype of cancer cells and consequently, may have tumor suppressor-like effects.
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PMID:Loss of transformed phenotype in cancer cells by overexpression of the uteroglobin gene. 1009 46

Cellular migration and invasion are critical for important biological processes including cancer metastasis. We previously reported that uteroglobin (UG), a multifunctional secreted protein, binds to several cell types inhibiting migration and invasion [G.C. Kundu, A.K. Z. Zhang Mandal, G. Mantile-Selvaggi, A.B. Mukherjee (1998) Uteroglobin (UG) suppresses extracellular matrix invasion by normal and cancer cells that express the high affinity UG-binding proteins. J Biol Chem. 273: 22819-22824]. More recently, we reported that HTB-81 adenocarcinoma cells, which do not bind UG, are refractory to UG-mediated inhibition of migration and invasion [Z. Zhang, G.C. Kundu, D. Panda, A.K. Mandal et al. (1999) Loss of transformed phenotype in cancer cells by overexpression of the uteroglobin gene. Proc Natl Acad Sci U S A. 96, 3963-3968]. Since UG shares several biological properties with lipocalin-1 that mediates some of its biological effects via its receptor (Lip-1R), we sought to determine whether UG might interact with Lip-1R and inhibit migration and invasion of HTB-81 cells. To address this question, we first transfected COS-1 cells, which do not bind UG, with a Lip-1R-cDNA construct and performed binding assays using 125I-human UG (hUG). The results show that hUG binds Lip-1R on these cells with high specificity. Further, transfection of HTB-81 cells with the same construct yielded 125I-hUG binding with high affinity (Kd=18 nM) and specificity. The hUG-Lip-1R interaction was further confirmed by transfecting HTB-81, HTB-30 and HTB-174 cells, which are refractory to UG-binding, with a green fluorescent protein (GFP)-Lip-1R-cDNA construct and testing for Lip-1R-hUG colocalization by fluorescence microscopy. Finally, we demonstrate that Lip-1R-hUG interaction on Lip-1R transfected HTB-81 cells renders them fully responsive to hUG-mediated inhibition of migration and invasion. Taken together, these results suggest that Lip-1R is at least one of the UG-binding proteins through which UG exerts anti-motility and anti-invasive effects.
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PMID:Interaction of uteroglobin with lipocalin-1 receptor suppresses cancer cell motility and invasion. 1642 71