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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
J Steroid Biochem Mol Biol 1996 Apr
PMID:The rat endometrial adenocarcinoma cell line RUCA-I: a novel hormone-responsive in vivo/in vitro tumor model. 880 92

Mammalian cells contain an intron-less myc gene, such as the rat s-myc gene and human myc L2 gene, which are expressed in rat embryo chondrocytes and human testis, respectively. Our recent findings demonstrated that s-Myc expression suppresses the growth activity and tumorigenicity of glioma cells, indicating that s-Myc acts as a negative regulator in tumor growth. In addition, we found that s-Myc overexpression can effectively induce apoptotic cell death in human and rat glioma cells without serum deprivation, which is distinct from c-Myc-mediated apoptosis.
Prog Mol Subcell Biol 1996
PMID:Myc-mediated apoptosis. 882 95

Molecular alterations play a key role in the pathogenesis of gastrointestinal cancers. In the present paper we describe relevant molecular alterations in human pancreatic adenocarcinomas. Overexpression of growth factor receptors (EGF receptor, c-erbB2, c-erbB3, TGF beta receptor I-III), growth factors (EGF, TGF alpha, TGF beta-1-3, aFGF, bFGF), adhesion molecules (ICAM-1, ELAM-1) and gene mutations (p53, K-ras, DCC, APC) are present in a significant number of these tumors. These changes stimulate tumor growth and enhance the metastatic behavior of pancreatic cancer cells and thereby may contribute to shorter postoperative survival following tumor resection.
J Mol Med (Berl) 1996 Jan
PMID:Pancreatic cancer: the potential clinical relevance of alterations in growth factors and their receptors. 883 68

Cancer of the prostate is the most frequent cancer and the second leading cause of cancer death in men in North America. The growth of Shionogi carcinoma-115 (SC-115) cells is highly sensitive to androgens, and this cell line is a well known experimental model of prostate cancer. The transplantable Shionogi carcinoma tumor was used to assess the influence of tumor size on the response to flutamide treatment. Two weeks after subcutaneous inoculation of tumor fragments in Shionogi mice, six groups of animals bearing SC-115 tumors ranging from 0.1 to 1.8 cm in diameter were treated with flutamide (1 mg, twice daily). The castrated mice received an androstenedione (delta4-dione) implant to mimic the human situation, where the adrenals produce precursor steroids which are transformed into androgens in peripheral intracrine tissues. After 16 days, treatment with flutamide inhibited tumor growth by 32 to 57% in the four groups of mice having tumors ranging from 0.1 to 1.0 cm in diameter at day 0, whereas no significant inhibitory effect was observed in larger tumors. The same treatment, however, caused potent inhibitory effects on other androgen-sensitive parameters, namely prostatic and seminal vesicle weight and kidney ornithine decarboxylase (ODC) activity, the effect on these parameters being similar in all groups of animals, irrespective of tumor size. Furthermore, when those larger tumors unresponsive to antiandrogenic treatment were cut into small fragments and inoculated into new groups of mice, the same treatment with flutamide efficiently inhibited tumor growth, treatment being started at tumor sizes of 0.1 to 0.3 cm in diameter. The present data clearly demonstrate that small tumors are highly sensitive to androgen deprivation, while loss of response develops with increasing tumor size, thus indicating that, for optimal efficacy, androgen blockade should be given at the early stages of prostate cancer.
J Steroid Biochem Mol Biol 1996 Aug
PMID:Large Shionogi tumors lose their responsiveness to flutamide treatment. 891 74

Prostaglandin A2 (PGA2) suppresses tumor growth in vivo, is potently antiproliferative in vitro, and is a model drug for the study of the mammalian stress response. Our previous studies using breast carcinoma MCF-7 cells suggested that p21(Waf1/Cip1) induction enabled cells to survive PGA2 exposure. Indeed, the marked sensitivity of human colorectal carcinoma RKO cells to the cytotoxicity of PGA2 is known to be associated with a lack of a PGA2-mediated increase in p21(Waf1/Cip1) expression, inhibition of cyclin-dependent kinase activity, and growth arrest. To determine if cell death following exposure to PGA2 could be prevented by forcing the expression of p21(Waf1/Cip1) in RKO cells, we utilized an adenoviral vector-based expression system. We demonstrate that ectopic expression of p21(Waf1/Cip1) largely rescued RKO cells from PGA2-induced apoptotic cell death, directly implicating p21(Waf1/Cip1) as a determinant of the cellular outcome (survival versus death) following exposure to PGA2. To discern whether p21(Waf1/Cip1)-mediated protection operates through the implementation of cellular growth arrest, other growth-inhibitory treatments were studied for the ability to attenuate PGA2-induced cell death. Neither serum depletion nor suramin (a growth factor receptor antagonist) protected RKO cells against PGA2 cytotoxicity, and neither induced p21(Waf1/Cip1) expression. Mimosine, however, enhanced p21(Waf1/Cip1) expression, completely inhibited RKO cell proliferation, and exerted marked protection against a subsequent PGA2 challenge. Taken together, our results directly demonstrate a protective role for p21(Waf1/Cip1) during PGA2 cellular stress and provide strong evidence that the implementation of cellular growth arrest contributes to this protective influence.
Mol Cell Biol 1996 Dec
PMID:Protective role of p21(Waf1/Cip1) against prostaglandin A2-mediated apoptosis of human colorectal carcinoma cells. 894 19

1. Which angiogenic growth factors actually mediate tumor growth in ethylnitrosourea (ENU)-induced gliomas in rats was examined. 2. In situ hybridization histochemistry with digoxigenin-labeled oligonucleotide probes was used to investigate the cellular expression and distribution of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNAs in ENU-induced gliomas. 3. Both VEGF and bFGF mRNAs were not detected in normal gial cells but in ENU-induced glioma cells. 4. Our results suggest that the growth of ENU-induced glioma may be regulated by multiple angiogenic growth factors and that these gliomas may proliferate by synthesizing such growth factors.
Cell Mol Neurobiol 1997 Feb
PMID:VEGF and bFGF mRNA are expressed in ethylnitrosourea-induced experimental rat gliomas. 911 6

The effect of lovastatin, a hypocholesterolemic drug, on tumor growth and desaturase activity was studied in a human lung mucoepidermoid carcinoma (HLMC) grown in nude mice. After administration of a diet supplemented with 25 mg% (w/w) lovastatin for 30 days the growth of HLMC was not inhibited. Liver and tumor phospholipid/cholesterol ratio was increased in lovastatin group but serum cholesterol was unaffected. Treatment with lovastatin increased delta 5 and delta 9 desaturation in tumor microsomes, whereas delta 6 desaturation did not change in tumors of treated mice. The changes were not reflected in the fatty acid composition of total tumor lipids.
Biochem Mol Biol Int 1996 Apr
PMID:Effects of lovastatin on the fatty acid desaturation in a human lung mucoepidermoid carcinoma grown in nude mice. 913 62

We have developed a novel murine mammary tumor system with variants representing different stages of tumor progression. The MXT-s parental cell line was established from a urethane-induced and hormone-sensitive mammary tumor. MXT-s parental cells are highly tumorigenic but poorly metastatic. MXT clones and variants were selected by either in vitro or in vivo procedures, and they differ in metastatic ability and 17 beta-estradiol dependency for tumor growth. The MXT-c1.1 and MXT-B2 cell lines produced lung metastasis after intravenous injection into 100% of syngenic mice, but only MXT-c1.1 cells were highly metastatic from intramammary tumors. The fingerprints obtained by arbitrarily primed-polymerase chain reaction demonstrated that the metastatic variants and clones had a common genetic background and resulted from clonal selection from the parental cell line. We studied whether the matrix metalloproteinase (MMP) profile is correlated with tumor progression and metastatic ability in the MXT tumor system. Gelatinases A and B were assayed in the cells, both by enzyme activity and mRNA expression. Gelatinase A was expressed in MXT-c1.1 cells, whereas MXT-B2 cells did not express either MMP. In contrast, the mammary fat pad tumors expressed both gelatinases. Membrane Type 1-MMP transcripts were also detected in MXT cells and tumors. Because the mRNA levels of gelatinase. A were low in MXT-B2 tumors, we suggested that exogenous gelatinase A bound the cell membranes of MXT-B2 cells in vivo. Indirect evidence was obtained in vitro by treatment of MXT-B2 cells with NIH/3T3 fibroblast-conditioned medium. After this treatment, we detected a gelatinolytic activity at M(r) 68,000 in the cell-membrane extract of MXT-B2 cells and an increase in migratory ability through type IV collagen matrices. On the other hand, Ha-ras gene dosage correlated positively with metastatic ability but not with either gelatinase A or gelatinase B expression. No significant differences were observed in the expression of stromelysin-1 and tissue inhibitors of MMP. Thus, in the MXT tumor system, the expression of gelatinase A or its cell association and Ha-ras gene dosage independently contribute to the metastatic phenotype.
Mol Carcinog 1997 May
PMID:Metastatic ability of MXT mouse mammary subpopulations correlates with clonal expression and/or membrane-association of gelatinase A. 918 Sep 29

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) binds and activates the aryl hydrocarbon receptor (Ah-R), an endogenous transcription factor that is expressed in the thymus. TCDD exposure leads, among other effects, to thymus atrophy and immunosuppression. We previously analyzed the interference of TCDD with differentiation processes in fetal thymus organ cultures and found that in the presence of TCDD, the proliferation rate of immature (CD4- CD8- and CD4- CD8+ HSA+) thymocytes is inhibited, whereas the maturation along the CD4/CD8 path is accelerated. Moreover, the differentiation of thymocytes is skewed by TCDD at < or = 40% (compared with approximately 15% without TCDD) of the CD8 single-positive subset of future cytotoxic T cells, and apparently more cells audition for and pass positive selection. The fetal murine thymus expresses functional Ah-R mRNA, as shown by reverse transcription-polymerase chain reaction and TCDD-inducible CYP1A1 and CYP1B1 expression. Because the differentiation of thymocytes is to a considerable extent controlled by cytokines and many cytokine genes are potential targets of the Ah-R due to Ah-R-binding elements (xenobiotic response elements) in their promoters, we analyzed the cytokine expression in fetal thymus organ culture exposed to TCDD. Fetal thymi were cultured from gestation day 15 for < or = 8 days, thus covering ex vivo the period after population of the thymus anlage until birth. We show with semiquantitative reverse transcription-polymerase chain reaction that more interleukin (IL)-1beta, IL-2, IL-6, tumor growth factor (TGF)-beta3, and tumor necrosis factor-alpha are produced in TCDD-exposed thymi, whereas other cytokines (e.g., TGF-beta1, PAI-2, or IL-4) are only slightly up- and down-modulated during the culture period or not modulated at all (e.g., IL-1beta, IL-7, interferon-gamma, and TGF-beta2).
Mol Pharmacol 1997 Jul
PMID:Cytokine gene expression during ontogeny in murine thymus on activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin. 922 9

We examined the in vivo effects of ONO-5046xNa, a specific neutrophil elastase (NE) inhibitor, on the growth of 2 non-small cell lung cancer cell lines, EBC-1 and PC-3, transplanted into severe combined immunodeficiency (scid) mice. The daily intraperitoneal injection of ONO-5046xNa (50 mg/kg/day) completely suppressed the tumor growth in EBC-1, a human squamous carcinoma cell line which produces immunoreactive NE. By contrast, in PC-3, a human adenocarcinoma cell line which is unable to produce immunoreactive NE, the ONO-5046xNa treatment caused delayed growth of the tumor. These findings suggest that ONO-5046xNa may have a clinical role in preventing the growth of human non-small cell lung cancer.
Res Commun Mol Pathol Pharmacol 1997 Aug
PMID:Neutrophil elastase inhibitor (ONO-5046-Na) inhibits the growth of human lung cancer cell lines transplanted into severe combined immunodeficiency (scid) mice. 934 34


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