Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A genetic linkage map of human chromosome 21 has been constructed using 22 anonymous DNA markers and five complementary DNAs (cDNAs) encoding the amyloid beta protein precursor (APP), superoxide dismutase 1 (SOD1), the ets-2 proto-oncogene (ETS2), the estrogen inducible breast cancer locus (BCEI), and the leukocyte antigen, CD18 (CD18). Segregation of RFLPs detected by these DNA markers was traced in the Venezuelan Reference Pedigree (VRP). A comprehensive genetic linkage map consisting of the 27 DNA markers spans 102 cM on the long arm of chromosome 21. We have confirmed our initial findings of a dramatically increased rate of recombination at the telomere in both females and males and of significantly higher recombination in females in the pericentromeric region. By comparing patterns of recombination in specific regions of chromosome 21 with regard to both parental sex and age, we have now identified a statistically significant downward trend in the frequency of crossovers in the most telomeric portion of chromosome 21 with increasing maternal age. A less significant decrease in recombination with increasing maternal age was observed in the pericentromeric region of the chromosome. These results may help in ultimately understanding the physical relationship between recombination and nondisjunction in the occurrence of trisomy 21.
 ...
PMID:A genetic linkage map of human chromosome 21: analysis of recombination as a function of sex and age. 134 93

Breast cancer development is associated with several genetic abnormalities. Loss of heterozygosity in the short arm of chromosome 11 has been observed in 30% of tumors. We found homozygosity at five chromosome 11 polymorphic loci in genomic DNA of the MCF-7 breast carcinoma cell line, suggesting a possible loss of one chromosome 11. We have studied the transformed and tumorigenic phenotypes of MCF-7 cells following introduction of a normal human chromosome 11 via microcell fusion. MCF-7/H11 cell hybrids, containing chromosome 11, showed in vitro characteristics similar to the parental cell line. However, tumorigenicity in athymic mice was completely suppressed. Since tumor formation by MCF-7 cells is estrogen dependent, we have analysed the expression of the estrogen receptor and of the estrogen-activated gene pS2. No difference was detected between the parental MCF-7 cells and the derived chromosome 11 cell hybrids, indicating that the mechanism of MCF-7 tumor suppression by chromosome 11-associated functions does not directly involve the estrogen/estrogen receptor molecular pathway.
 ...
PMID:Suppression of tumorigenesis by the breast cancer cell line MCF-7 following transfer of a normal human chromosome 11. 140 42

Tumoral biological markers of breast cancer expand the predictive value of conventional prognostic factors, such as tumor size, axillary lymph node status, and histoprognostic grade. They include tumor estrogen and progesterone receptor levels, flow cytometric DNA analysis, to convey a prognostic value. Expression of the product of the gene pS2, which reflects the functional integrity of the estradiol receptor, indicates a good prognosis. In contrast, presence of growth factor receptors, such as the EGF receptor, or amplification of the HER2/neu or INT2 oncogene indicate a poor prognosis. Study of protein gp 170 and GST-pi predicts the response of tumors to chemotherapy, while the study of the potential doubling time (Tpot) provides an indication of the renewal capacity of the tumor. Markers of tumor invasiveness and metastatic potential include proteases (activators and inhibitors) produced either by tumor cells or by the cells of the stroma, gene nm 23, and membrane fatty acids. The place of the last markers in patients' treatment is not known yet. The knowledge of the tumor biological parameters along with clinical features should provide an accurate prediction of the aggressiveness of the tumor, allowing the best adjustment of treatment with the expected behavior of the disease.
 ...
PMID:[Intratumoral biological markers in breast cancers]. 148 91

A human cDNA corresponding to the porcine pancreatic spasmolytic protein (PSP) was isolated, and the recombinant clone was originally termed hSP for human spasmolytic protein. Later, the term SML1 for spasmolysin was suggested for the human gene. This protein shows a remarkable sequence homology to pS2, a protein coded by an estrogen-induced gene isolated from the breast carcinoma cell line MCF-7. Although, at the DNA level, the gene sequences pS2 and hSP/SML1 display insufficient homology for cross-hybridization, their expression in tumor cells occurs with remarkable coordination. The human pS2 gene sequence has been assigned to chromosome 21, and we have therefore attempted to map the hSP/SML1 gene by using cDNA and Southern blotting of genomic DNAs from a panel of human-rodent somatic cell hybrids carrying different complements of human chromosomes. Interestingly, the hSP/SML1 gene is also localized on chromosome 21.
 ...
PMID:Assignment of the gene for human spasmolytic protein (hSP/SML1) to chromosome 21. 151 87

The progressive myoclonus epilepsies (PME) are a heterogeneous group of rare genetic disorders. Unverricht-Lundborg disease and Lafora's disease are two major classic forms of PME. We recently assigned the gene for Unverricht-Lundborg disease (EPM1) to human chromosome 21 band q22.3. We have now refined the localization of EPM1 by linkage analysis between the disease phenotype and nine DNA markers in 13 Finnish families. Loci MX1 and CD18 flank the EPM1 interval, which spans a distance of about 3.5 megabases. In this 20-centimorgan interval, no recombinations were detected between EPM1 and marker loci BCEI, D21S19, D21S42, D21S113, D21S154, and PFKL. Within this interval a maximum multipoint lod score of 11.04 was reached at loci D21S154-PFKL. In two Swedish families with Unverricht-Lundborg disease no recombinations were detected. In three Italian families with Lafora's disease the linkage results suggested that EPM1 is not the locus for Lafora's disease.
 ...
PMID:Linkage studies in progressive myoclonus epilepsy: Unverricht-Lundborg and Lafora's diseases. 164 Nov 51

Progressive myoclonus epilepsy of Univerricht-Lundborg type is a clinically defined entity among the progressive myoclonus epilepsies. It is an autosomal recessive disorder. The underlying biochemical defect is unknown. We used linkage analysis to localize the gene in 12 families with the aid of polymorphic DNA markers. Close linkage was detected with three markers on distal chromosome 21. The loci BCEI and D21S154 gave the highest positive logarithm-of-odds (lod) scores of 5.49 and 4.25, respectively, at zero recombination. The third locus, D21S112, gave a lod score of 6.91 at a recombination fraction of 0.034. There was no evidence of heterogeneity. Multipoint lod scores calculated against a fixed map of the three marker loci gave a maximum four-point lod score of 10.08 at a location of the disease gene at 6.0 centimorgans distal to locus BCEI and 0.8 centimorgan proximal to locus D21S154. As markers BCEI and D21S154 have previously been localized to 21q22.3 by physical methods, our findings place the EMP1 gene locus (for progressive myoclonus epilepsy of the Unverricht-Lundborg type) in chromosome 21 band q22.3. This finding provides an opportunity to test several other epilepsy phenotypes, particularly the so-called Ramsay Hunt syndrome, for linkage to the same locus. It also is a starting point toward isolating and characterizing the gene and its protein product.
 ...
PMID:Localization of a gene for progressive myoclonus epilepsy to chromosome 21q22. 167 90

To study the mechanism of regression of human mammary cancer following estrogen ablation, estrogen-responsive MCF-7 human mammary adenocarcinoma cells were inoculated into ovariectomized female nude mice supplemented with exogenous 17 beta-estradiol (E2) via an E2 implant. Implants were then removed when MCF-7 tumors were 400 mm3 in size. Removal of the E2 implants resulted in a 50% tumor regression by 2 weeks following E2 ablation. Associated with this regression is a rapid (i.e., within 1 day following E2 ablation) enhanced expression of the transforming growth factor beta 1 and TRPM-2-genes, two genes the expression of which has been previously demonstrated to be enhanced in a variety of cell types induced to undergo programmed cell death (i.e., apoptosis). The enhanced expression of transforming growth factor beta 1 and TRPM-2 is not a nonspecific response since the expression of other genes, like c-fos, c-H-ras, and pS2, decrease following E2 ablation. Fragmentation of tumor DNA into nucleosomal oligomers and histological appearance of apoptotic bodies are characteristic early events that precede the dramatic reduction in tumor volume following E2 ablation. These results demonstrate that the regression of MCF-7 human mammary cancers in nude mice following estrogen ablation is due to a sequence of biochemical and morphological changes that result in both the cessation of cell proliferation and activation of programmed death or apoptosis of these MCF-7 cancer cells. Clarification of the biochemical pathway involved in the activation of this programmed cell death should identify new targets of therapy for even estrogen-independent human mammary cancer cells.
 ...
PMID:Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. 189 37

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) (10 nM) produce a marked reduction in the growth, measured by thymidine uptake, of MCF-7 cells in full growth medium, but had only a small effect on MDA-MB-231 and T47D cells. Bryostatin alone also inhibited growth but to a lesser extent than seen with TPA. The effect of TPA on MCF-7 cells was partially reversed by bryostatin, added simultaneously or after TPA, suggesting bryostatin does not simply mimic TPA in this system. Even though both are believed to act via effects on protein kinase C, bryostatin appears to act as antagonist to the effect of TPA as well as a partial agonist on its own. When the oestrogen receptor positive MCF-7 and T47D cells were maintained in charcoal stripped serum, the increase in DNA synthesis on stimulation with oestradiol was inhibited with 50 nM TPA in MCF-7 cells but not in T47D cells. The effects of these treatments on the expression of two well characterised oestrogen responsive genes pNR2(pS2) and pNR100 (Cathepsin-D) were examined. Rather than preventing transcription of these oestrogen responsive genes, TPA alone increased pNR2 and pNR100 levels in MCF-7 cells and the combined effect of oestradiol and TPA had a marked synergistic effect in increasing the transcript levels of these genes. In T47D cells pNR2 transcripts were not detected and the increase in pNR100 mRNA levels were not affected by TPA. We conclude that the inhibitory effects of TPA on the growth stimulation of MCF-7 cells by oestradiol was not due to a general inhibition of the expression of oestrogen responsive genes. An alternative possibility examined was that the growth inhibitory effect of TPA on MCF-7 cells might be due to stimulation of TGF-beta 1, acting as an autocrine inhibitory growth factor. Oestradiol treatment of MCF-7 cells reduced the levels of TGF-beta 1 mRNA whereas TPA produced a marked increase. The combined effect of TPA and oestradiol further increased TGF-beta 1 mRNA above the levels seen with TPA alone. Bryostatin had little effect on TGF-beta 1 expression either alone or in combination with oestradiol. These observations are consistent with the hypothesis that the inhibitory effect of TPA on MCF-7 cells may be partly due to autocrine inhibition by TGF-beta 1.
 ...
PMID:Phorbol ester and bryostatin effects on growth and the expression of oestrogen responsive and TGF-beta 1 genes in breast tumour cells. 191 Dec 15

Several vectors were used to express the complementary DNA for breast cancer estrogen-induced protein BCEI (also called pS2) in Escherichia coli. The best results were obtained by using the pUR 290 expression vector after deletion of the sequence encoding the signal peptide of the protein. In these conditions, beta-galactosidase-BCEI/pS2 fusion protein accounted for approximately 20% of total proteins in bacterial extracts. It was purified by chromatography on DEAE-Trisacryl or by gel electrophoresis and electroelution. Polyclonal antibodies were obtained by immunization of rabbits and goats, and monoclonal antibodies were raised in mice. Two types of monoclonal antibodies were obtained: one class recognized the native protein and was very efficient for the immunoprecipitation and immunopurification of the protein from breast cancer cells; a second class recognized the denatured protein and was especially effective for immunoblot studies. BCEI/pS2 could be detected by immunocytochemistry in breast cancer biopsies using monoclonal antibodies on frozen or paraffin-embedded sections. One of the antibodies (mBCEI11) exhibited high affinity for the protein and could be used at 1.9 micrograms/ml concentration for immunolabeling of histological sections. The mBCEI11 antibody was used in immunoaffinity chromatography to purify the peptide in a single step from culture media of estrogen-treated MCF-7 cells.
 ...
PMID:Monoclonal antibodies against native ant denatured forms of estrogen-induced breast cancer protein (BCEI/pS2) obtained by expression in Escherichia coli. 218 May 69

A complementary DNA library was constructed from RNA of estrogen-stimulated MCF-7 cells and screened for estrogen-regulated sequences. Four different messenger RNA sequences of varying abundance were isolated. Two of the sequences (pNR-3 and pNR-4) were induced approximately 2-fold, while the other two (pNR-1 and pNR-2) were induced at least 8-fold. The induction of both pNR-1 and pNR-2 requires similar physiological concentrations of estradiol and is near maximal at 10(-10) M. An increase in the levels of the RNAs is seen after 30 min of estrogen treatment, but pNR-1 reaches its maximal concentration faster than pNR-2. pNR-1 and pNR-2 were not expressed in all human breast cancer cell lines tested. pNR-1 was expressed and regulated by estrogen in the estrogen receptor-positive cell lines, MCF-7, T-47D, and ZR 75, whereas pNR-2 was not expressed in the T-47D cell line. pNR-1 and pNR-2 were not detected in two estrogen receptor-negative cell lines (BT20 and HBL 100). As the proliferation of the MCF-7, T47D, and ZR 75 cell lines is stimulated by estradiol, pNR-1 may provide a useful marker of hormone-responsive breast cancer.
 ...
PMID:Cloning of estrogen-regulated messenger RNA sequences from human breast cancer cells. 243 Jun 88


1 2 3 4 5 6 7 8 9 10 Next >>