Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoic acid (RA) inhibits proliferation of estrogen receptor (ER)-positive human breast cancer cells, but not the growth of ER-negative cells. We have shown previously that ER-positive cells express higher levels of retinoic acid receptor (RAR) alpha, suggesting that RAR alpha gene expression may be regulated in breast cancer cells by estrogens. We here report that estradiol (E2) increases RAR alpha mRNA in a time- and concentration-dependent manner resulting in a marked increase in RAR alpha protein expression, and present evidence that RAR alpha 1 is the only known isoform of RAR alpha regulated by E2 in breast cancer cells. In parallel we demonstrate that ER-positive cells exhibit greater RA sensitivity in the presence of E2, suggesting that E2-induced expression of RAR alpha 1 is involved in growth inhibition by RA. To directly investigate the role of RAR alpha 1 in RA-mediated growth inhibition, we introduced RAR alpha 1 expression vectors into RA-resistant and ER-negative MDA-MB-231 cells. The RAR alpha 1-transfected cells were growth inhibited by RA, while mock- and untransfected cells were unresponsive. Together, our data indicate that adequate levels of RAR alpha 1, either generated by introduction of expression vectors or endogenously induced by estrogens, are required for growth inhibition of breast cancer cells by RA.
Mol Cell Endocrinol 1995 Mar
PMID:Retinoic acid receptor alpha 1 isoform is induced by estradiol and confers retinoic acid sensitivity in human breast cancer cells. 778 18

In previous experiments, rabbits were injected with heterologous proteins reacted with MDA, and produced antibodies cross-reacting with other MDA-modified proteins (MPr), but not with the corresponding native ones (Pr). It was concluded that these antibodies (AbAIP) recognized epitopes including 1-amino-3-imino-propene (AIP) bridges resulting from reactions of MDA with primary amino groups of proteins. In the present work, mice were injected with autologous MDA-modified albumin (MAI) or with heterologous MPr. Mice immunized with MAI developed an immune response leading to an increased production of AbAIP, which clearly indicates that such a response may occur even with an autologous MPr.
Biochem Mol Biol Int 1994 Aug
PMID:Immunization of mice with proteins reacted with malonic dialdehyde (MDA): comparison between autologous and heterologous modified proteins. 784 16

We sought to determine whether the hepatocyte growth factor/scatter factor (HGF/SF)- and keratinocyte growth factor-receptor systems were expressed in normal breast cells, breast carcinoma cell lines, normal breast tissues, and breast cancer tissues. Reverse transcriptase-polymerase chain reaction and hot blotting were used to detect HGF, HGF/SF (met) receptor, KGF, and KGF receptor mRNAs in human mammary epithelial (HME) and stromal (HMS) cells. We also examined breast carcinoma (MDA-MB-157, SCC 38, and SCC 70) and spontaneously immortalized breast epithelial (HMT 3522) cell lines, as well as normal breast and breast carcinoma tissues. PCR products were also confirmed by nucleic acid sequencing. The effects of HGF and KGF, compared to EGF and heparin-binding EGF, on the proliferation of normal human mammary epithelial cells in serum-free defined medium was determined by cell counting. HGF and KGF mRNAs were detected in HMS cells, but not HME cells. KGF receptor mRNA was detected in HME cells, but not HMS cells. HGF/SF receptor mRNA was detected in both HME and HMS cells. mRNAs were also detected in normal breast and breast carcinoma tissues, as well as breast carcinoma and transformed breast epithelial cell lines. Alternative cDNA sequences that are predicted to code for a soluble KGF receptor and a membrane bound, truncated HGF/SF receptor were detected in breast epithelial cells and breast tissues. HGF and KGF maintained viability and stimulated proliferation of HME cells.
Cell Mol Biol Res 1994
PMID:Hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and their receptors in human breast cells and tissues: alternative receptors. 786 34

Using reverse transcription (RT)/PCR we have shown that four breast cancer cell lines expressed oestrogen receptor (ER) mRNA, irrespective of whether they were assessed as ER-positive (MCF-7 and BT-474) or ER-negative (MDA-MB-231 and BT-20) by enzyme immunoassay (EIA). In addition to the wild type (WT) form, they were all found to express the exon 5-deleted variant (V) form of ER mRNA by RT/PCR; this is thought to code for a truncated constitutively active protein. By Northern blot analysis only the ER-positive cell lines (MCF-7 and BT-474) were found to express detectable levels of ER mRNA. Oestradiol-induced growth was found only in the ER-positive (by EIA) cell lines. These results confirm that the differences between ER-positive and ER-negative cell lines are quantitative rather than qualitative. As low levels of ER mRNA could be detected by RT/PCR, this may reflect the greater sensitivity of this approach. The presence of exon 5-deleted V form ER mRNA in addition to the WT form in all four breast cancer cell lines may allow these lines to be used to assess differential regulation of transcription and the impact of this on their oestrogen dependence.
J Mol Endocrinol 1994 Dec
PMID:Detection of wild type and exon 5-deleted splice variant oestrogen receptor (ER) mRNA in ER-positive and -negative breast cancer cell lines by reverse transcription/polymerase chain reaction. 789 44

In this study the role of high density lipoproteins in lipoprotein peroxidation process was investigated. Under basal conditions, HDL isolated from human plasma or from total lipoprotein fraction (density > 1.21) using precipitation technique carried nearly 35-40% of the total plasma fatty acid peroxidation product (measured as malonaldehyde, MDA). HDL associated MDA was reduced to < 20% when HDL was isolated by ultracentrifugation from plasma treated with Cu++. Under these conditions, 45% of the cholesterol peroxidation products (oxysterols) were associated with HDL. HDL isolated from Cu++ treated plasma significantly lost its ability to inhibit LDL peroxidation. These results suggest that HDL plays an important role in lipid peroxidation a) by carrying significant amounts of cholesterol and lipid peroxidation products, and b) its ability to inhibit LDL oxidation is compromised when HDL itself is oxidized.
Biochem Mol Biol Int 1994 Jul
PMID:Significant association of lipid peroxidation products with high density lipoproteins. 798 57

5-Fluorouracil (5FU), an antimetabolite often used for the treatment of breast cancer, binds to and inactivates the enzyme thymidylate synthase (TS). Measurement of TS levels may be useful in examining resistance to 5FU, but current methods involving ligand binding assays present considerable problems due to the low basal level of this enzyme in many tissues. Therefore, a semiquantitative polymerase chain reaction (PCR) technique to measure TS RNA concentration in breast tumour cell lines has been developed with potential for measuring TS RNA levels in individual breast tumours. Using less than 1 microgram of total RNA, we determined that the T47D breast cancer cell line expressed TS levels 1.3 to 4.4 times lower than those of four other breast cancer cell lines, MCF-7, MDA-MB-468, MDA-MB-231, and MDA-A1R. Using the MCF-7 cell line as a representative of relatively high TS expression, the relationship between the S-phase fraction (SPF), and TS levels in MCF-7 and T47D cells was next examined because cell cycle kinetics can also influence drug response. TS expression was directly related to SPF. MCF-7 cells had a higher SPF, corresponding to their higher TS level relative to T47D cells. Lastly, 5FU sensitivity was assayed for and it was found that MCF-7 cells were more sensitive to 5FU than T47D, despite having higher TS levels. A semiquantitative technique for assessing TS RNA expression by PCR in breast cancer cell lines has been demonstrated. In the cell lines tested, there was no direct relationship between TS level and 5FU sensitivity, though there was a direct relationship between cell proliferation and sensitivity to 5FU.
Mol Cell Probes 1994 Feb
PMID:Evaluation of thymidylate synthase RNA expression by polymerase chain reaction. 802 10

We have studied the effect of Mg deficiency on both tissue mineral content and liver oxidative status. Male Wistar rats kept for eight weeks on a Mg-deficient diet (Mg 152ppm) quickly developed a severe plasma Mg deficiency (73% decrease). The content of Cu and Fe significantly increased in different tissues following the treatment. Liver glutathione, CuZn-superoxide dismutase, and vitamin E were significantly reduced (by about 16%, 18% and 30% respectively). Lipid peroxidation, induced in vitro by NADPH/ADP-Fe3+ and measured as MDA formation, increased by about 100% after 20 min incubation in liver microsomes isolated from Mg-deprived rats. The alterations found in the content of transition metals and in the level of both cytosolic and membrane antioxidants, as well as the higher sensitivity of liver microsomes to lipid peroxidation in vitro, are consistent with an oxidative stress occurring in vivo in the tissues of Mg-deficient animals.
Biochem Mol Biol Int 1994 Apr
PMID:Mg deficiency induces mineral content changes and oxidative stress in rats. 806 40

The effects of age and hypertension on the antioxidant defence systems and the lipid peroxidation in rat isolated hepatocytes were studied. Four different age groups (1, 3, 6 and 12 months) were considered in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Age-associated changes were observed on vitamin E status, glutathione (GSH) level, MDA formation and glutathione peroxidase (GSH-Px) activity in both strains. Maximal levels or activities of these parameters were found at 3 and 6 months, except for MDA which was low at 3 months. Then, a fall was observed at 12-month-old compared to 6-month values. In addition, GSH-Px activity was significantly lower in SHR than in WKY rats, except at the age of one month. The decrease of this enzyme activity could induce an increased cellular generation of radical species and lipid peroxidation, which might be link to hypertension.
Mol Cell Biochem 1994 Mar 16
PMID:Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats. 807 5

Transforming growth factor (TGF) beta is a potent regulator of cell proliferation and may play a role in breast cancer cell growth. We have evaluated the regulation of TGF beta 1, TGF beta 2, and TGF beta 3 mRNAs by 17 beta-estradiol (E2) and 4-hydroxytamoxifen (MOH) in estrogen receptor-positive (ER(+)) MCF-7 and estrogen receptor-negative (ER(-)) MDA-MB-231 human breast cancer cells. We also determined the effect of TGF beta 1, TGF beta 2, and TGF beta 3 on the proliferation of these cells. Cells were deprived of estrogen before the addition of hormones, and mRNA was measured by Northern blot analysis. We found that MCF-7 cells expressed mRNAs of all three TGF beta species. Treatment of MCF-7 cells with 10(-10) M E2 for 7 days resulted in a dramatic decrease in the TGF beta 2 and TGF beta 3 mRNA levels, but not in the TGF beta 1 mRNA level. MOH was found to block these effects. In addition, the regulation of TGF beta 2 and beta 3 gene expression occurs at both transcriptional and post-transcriptional levels. There is an inverse correlation between E2-induced growth and levels of TGF beta 2 and TGF beta 3 mRNA. In contrast to MCF-7 cells, MDA-MB-231 cells expressed TGF beta 1 and TGF beta 2 mRNAs but TGF beta 3 mRNA was not detected, and the TGF beta 1 and TGF beta 2 mRNAs were not regulated by estrogens or antiestrogens.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1993 Nov
PMID:Regulation of the levels of three transforming growth factor beta mRNAs by estrogen and their effects on the proliferation of human breast cancer cells. 814 93

In most human breast cancer cell lines, insulin, via its own receptor, stimulates cell growth. However, in MDA-MB231 breast cancer cells, insulin at concentration as high as 100 nM has no effect on cell growth, although insulin receptors (IRs) are overexpressed in these cells (29.1 ng IR/10(6) cells), and IR binding characteristics are similar to other breast cancer cell lines. IR tyrosine kinase activity is markedly reduced both in intact MDA-MB231 cells and in isolated IRs purified on a wheat germ agglutinin affinity column. MDA-MB231 cells contain a factor that inhibits both basal and insulin-stimulated IR tyrosine kinase activity in a concentration-dependent manner. This inhibitory activity copurifies with the IR on insulin-Sepharose affinity chromatography and is also effective against the tyrosine kinase activity of the IR-related insulin-like growth factor-I receptor and the oncoprotein v-abl but is ineffective against c-src tyrosine kinase activity. It is possible, therefore, that this tyrosine kinase inhibitor plays a role in regulating the mitogenic potential of the IR in some human breast cancers.
Mol Endocrinol 1993 Dec
PMID:Insulin-resistant MDA-MB231 human breast cancer cells contain a tyrosine kinase inhibiting activity. 814 72


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