Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently established and characterized two rat endometrial adenocarcinoma cell lines which we called RUCA-I and RUCA-II. Despite high estrogen receptor levels neither cell line responded to estradiol in conventional cell culture conditions on plastic and in the presence of charcoal stripped fetal calf serum. We further demonstrated that culturing of these cells on a reconstituted basement membrane induced the estrogen responsiveness for both proliferation and gene expression. Particularly, the expression of components of the complement C3 system, which represent major estradiol inducible proteins in the rat uterus in vivo, were found to be under the control of estrogens and antiestrogens. In this paper the search for estrogen repressed proteins is reported. For this purpose secretory proteins of RUCA-I cells were metabolically labelled with 35S-methionine and tested for the presence of estrogen-repressed, antiestrogen-inducible protein species. Analyzing cell culture supernatants of RUCA-I cells by polyacrylamide gel electrophoresis under reducing conditions a protein with an apparent size of approx. 250-270 kDa became conspicuous. The formation and secretion of this protein was suppressed by estradiol and induced by the antiestrogen ICI 164384. Gel electrophoresis performed under non-reducing conditions and hyaluronidase digestion showed that this estrogen-repressed protein represents a dimeric glycoprotein. By immunoprecipitation this glycoprotein was identified as fibronectin. Investigations of steady state mRNA levels of fibronectin by rtPCR suggested a post-transcriptional regulation of this molecule by estradiol. This is the first report on repression of components of the extracellular matrix by estradiol and induction by the complete antiestrogen ICI 164384. The consequences of this finding in regard to growth and invasion of endometrial tumors are discussed.
 ...
PMID:Fibronectin is an estrogen-repressed protein in RUCA-I rat endometrial adenocarcinoma cells. 766 86

The recently established, estrogen receptor positive rat endometrial adenocarcinoma cell line RUCA-I was tested for estrogen responsiveness in vivo and in vitro. In vivo, 10(6) RUCA-I cells were injected subcutaneously into intact, ovariectomized, or ovariectomized, estradiol-substituted syngenic DA/Han rats. All animals developed well differentiated endometrial adenocarcinoma, that had metastasized to peripheral lymph nodes and into the lung. Ovariectomy reduced tumor and lymph node weight, as well as number of lung metastases significantly compared to controls. In another series of experiments, treatment with the pure anti-estrogen ZK 119010 basically gave the same results as seen in ovariectomized animals, whereas tamoxifen treatment had no effect on metastasis of RUCA-I cells. These findings clearly demonstrate the estrogen dependency of growth and metastasis of RUCA-I cells in vivo. In vitro, we assessed the estrogenic and anti-estrogenic potency of various anti-estrogens, thereby investigating their effects on the expression of components of the complement C3 complex as an estradiol-induced protein and on the expression of fibronectin as an estrogen-repressed protein. Evaluating the relative anti-estrogenic potency of these anti-estrogens we found that ICI 164384 and ICI 182780 behaved as complete antagonists in vitro. Tamoxifen, like estradiol, stimulated complement C3 production and repressed fibronectin expression and has to be regarded as an agonist in this particular in vitro system. ZK 119010 if given alone had no significant influence on the biosynthesis of complement C3 and of fibronectin if compared to the unstimulated control. In addition, another estrogen dependent parameter was identified. Estrogen and anti-estrogen treatment affected glycosylation of complement C3 components. After estradiol treatment predominantly the higher glycosylated epitope of complement C3 became detectable, which could be transformed into the low molecular weight epitope by treatment with hyaluronidase. Finally, we compared the anti-proliferative effects of ICI 164384 and of tamoxifen in vitro. Both anti-estrogens slightly inhibited the growth of RUCA-I rat endometrial adenocarcinoma cells. In conclusion, RUCA-I cells represent a powerful, endometrial derived experimental model to test the agonistic and antagonistic properties of anti-estrogens on growth and metastasis in vivo and on gene expression in vitro. The effects of the tested anti-estrogens on gene expression of RUCA-I cells were found to be useful in predicting their effectiveness on tumor growth in vivo.
 ...
PMID:The rat endometrial adenocarcinoma cell line RUCA-I: a novel hormone-responsive in vivo/in vitro tumor model. 880 92