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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The estrogenic and antiestrogenic activities of tamoxifen and 4-hydroxytamoxifen have been measured on the expression of two estrogen-regulated RNAs (pNR-1 and pNR-2) in the MCF7 human breast cancer cell line cultured in phenol red-free medium. The two antiestrogens increased the level of the pNR-1 RNA to about 80% of the estradiol-induced level, and the induction by estradiol was not significantly antagonized by either antiestrogen. In contrast, the pNR-2 mRNA was only increased to about 10% of the estradiol-induced level, and its induction by estradiol was antagonized by both tamoxifen and 4-hydroxytamoxifen. Thus, the two RNAs respond in dramatically different ways to these antiestrogens. 4-Hydroxytamoxifen and estradiol have similar affinities for the estrogen receptor; however, the induction of both RNAs by 4-hydroxytamoxifen required a 10-fold higher concentration than estradiol for maximum agonist activity, and a 500-fold molar excess was required to antagonize the induction by estradiol. Tamoxifen has a 20-100-fold lower affinity than estradiol for the estrogen receptor. A 200-fold higher concentration was required for maximum agonist activity and a 10,000-fold molar excess to antagonize the induction by estradiol. These results emphasize the complexity of antiestrogen action in human breast cancer cells.
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PMID:Effects of tamoxifen and 4-hydroxytamoxifen on the pNR-1 and pNR-2 estrogen-regulated RNAs in human breast cancer cells. 282 72

The BCEI gene codes for a small secreted protein and is expressed in the human mammary tumour cell line MCF7 under oestrogen control and in some breast cancers. We have mapped the gene to chromosome 21 using a panel of somatic hybrid lines, and in situ hybridization has allowed a precise assignment to band 21q223. Two restriction fragment length polymorphisms (RFLP) are described that should be of use in linkage or population studies to test a possible involvement of the BCEI gene in genetic predisposition to breast cancer. This gene should also be a useful marker for the genetic and physical mapping of chromosome 21, and for a better definition of the region involved in the clinical phenotype of Downs syndrome.
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PMID:Chromosome localization and polymorphism of an oestrogen-inducible gene specifically expressed in some breast cancers. 289 54

A cDNA library has been constructed from the poly(A)+ mRNA of oestrogen-stimulated ZR-75-1 human breast cancer cells. Screening by differential hybridization has identified eight clones which are stimulated between 4- and 16-fold by oestrogen. Two clones (pLIV-1) that are stimulated 4-fold, hybridize to three different mRNA species. A further five recombinants encode for a mRNA 600 bp long which is induced greater than 16-fold and have been shown to cross-hybridize to the oestrogen-responsive clone, pS2, isolated from the MCF-7 breast cancer cell line. Oestradiol was shown to be without detectable effect upon the expression of mRNA for dihydrofolate reductase, which is reported to be oestrogen regulated in MCF-7 cells. Actin gene expression is also unresponsive to oestradiol in ZR-75-1 cells. These results suggest that pLIV-1 represents a previously unidentified mRNA that may be involved in the oestrogen-regulated growth of ZR-75-1 human breast cancer cells.
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PMID:Effects of oestrogen on the expression of a 4.4 kb mRNA in the ZR-75-1 human breast cancer cell line. 290 3

The role of estrogen in the growth of human breast cancers has been investigated at two levels. First, we have studied the pS2 gene, whose transcription is stimulated by estrogen in the human breast cancer cell line, MCF-7. The pS2 gene product is a small, secreted polypeptide currently of unknown function, but with structural features similar to some growth factors. The expression of the pS2 gene has so far been detected only in MCF-7 cells and some breast cancer biopsies. Preliminary studies indicate that pS2 is a potential marker for hormone-dependent breast cancer. Ongoing studies will continue to focus on the implicated role of pS2 in the estrogen-mediated growth of breast cancers and its possible use as a marker for estrogen-dependent tumors. Second, we have analyzed the structure and function of the human ER. The receptor stimulates pS2 gene transcription by interacting with an ERE in the 5'-flanking region of that gene. A mutational analysis of the receptor protein has localized a DNA-binding domain, which determines target gene specificity, and a hormone-binding domain. These domains appear to be the only two regions of the receptor which are absolutely required for the transcription-activating function of the ER in transfection assays with reporter plasmids. The N-terminal region of the protein (regions A and B), which is necessary for increasing the efficiency of gene expression using the pS2 ERE, but not a vitellogenin ERE, may also play a role in transcription activation. Further progress in the characterization of the ER functional domains will require studies on target genes in a more physiological chromatin environment, as well as detailed physical analyses of receptor structure.
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PMID:Structure and function of the pS2 gene and estrogen receptor in human breast cancer cells. 290 50

The human pS2 gene is specifically expressed under estrogen transcriptional control in a subclass of estrogen receptor-containing human breast cancer cells. The pS2 gene encodes an 84-amino acid protein that is secreted after signal peptide cleavage. The distribution of pS2 protein in normal human tissues was studied with antibodies to pS2; pS2 was specifically expressed and secreted by mucosa cells of the normal stomach antrum and body of both female and male individuals. Moreover, no estrogen receptor could be detected in these cells, indicating that pS2 gene expression is estrogen-independent in the stomach. The function of the pS2 protein in the gastrointestinal tract is unknown. However, the pS2 protein is similar in sequence to a porcine pancreatic protein that has been shown to inhibit gastrointestinal motility and gastric secretion.
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PMID:Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa. 304 93

The hormone-dependence of some human breast cancers is well recognized. However, the molecular mechanisms responsible for the growth stimulation of these cancers by oestrogens are still poorly understood. With the hope of elucidating these mechanisms, we have recently cloned and studied the structure-function relationship of the human oestrogen and progestin receptors, and also undertaken a study aimed at characterizing genes whose expression is controlled by oestrogens in hormone-dependent breast cancers. We review here our findings concerning one of these genes and its expression products, the pS2 gene. We discuss also whether a systematic determination of pS2 gene expression in breast cancer biopsies could be useful to establish a new biochemical classification of these cancers which may be useful to improve the diagnosis of hormone-dependent cancers.
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PMID:[Specific expression of human pS2 gene in breast cancer]. 314 28

Human epidermal growth factor-like immunoreactive factor (designated as EGF-LI) synthesized and secreted by human breast cancer cells, strain MCF-7, was isolated in pure form. Thirty-seven micrograms of EGF-LI was purified by anion-exchange, gel permeation, and reverse-phase high-performance liquid chromatography from 2 liters of serum-free medium conditioned by the cells. The sequence of the first 36 amino acids from the N-terminus was determined with a gas-phase protein sequencer. Computer-assisted screening revealed, quite unexpectedly, this sequence to be completely identical to that of the translational product encoded by pS2, the human estrogen-responsive gene, over the region extending from residue 25 to 60 (Jakowlew, S. B. et al. (1984) Nucleic Acids Res., 12, 2861-2878).
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PMID:Identification of a polypeptide secreted by human breast cancer cells (MCF-7) as the human estrogen-responsive gene (pS2) product. 326 81

The expression of the pS2 gene, which is induced by estrogen in the breast cancer cell line MCF-7, has been investigated in breast cancers by using pS2 mRNA determination in tumor specimens and immunocytochemistry to identify pS2 protein in paraffin-embedded sections. Using these assays we show that determination of pS2 gene expression allows the definition of subclasses of estrogen-receptor-containing breast cancers that may be used to more precisely identify estrogen-dependent tumors. Tumor specimens have also been analyzed for the presence of mRNAs for the estrogen receptor and for the ERBB2 oncogene. No evidence for the presence of truncated forms of estrogen-receptor mRNA has been found, and overexpression of the ERBB2 oncogene did not correlate with the steroid receptor status or pS2 gene expression.
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PMID:Specific expression of the pS2 gene in subclasses of breast cancers in comparison with expression of the estrogen and progesterone receptors and the oncogene ERBB2. 332 Oct 71

Our laboratory has reported previously the cloning of a complementary DNA termed pS2, corresponding to a messenger RNA (mRNA) whose synthesis is induced by estrogen in the human breast cancer cells MCF-7. Examination of the possible open reading frames of this complementary DNA has led to the prediction that the pS2 protein could be a secreted polypeptide of either 58 or 63 amino acids in length. Using a rabbit antiserum prepared against a synthetic peptide corresponding to the last 31 amino acids of the putative protein, we show that a protein with the expected migration during sodium dodecyl sulfate gel electrophoresis can indeed be immunoprecipitated from either the culture medium of MCF-7 cells grown in the presence of labeled amino acids or the in vitro translation products of MCF-7 poly(A) RNA enriched in pS2 mRNA. Furthermore, in vivo and in vitro differential amino acid labeling allows us to conclude that the mature pS2 protein is probably secreted as a 58 amino acid long peptide. Finally, we show that pS2 protein synthesis is induced in MCF-7 cells by estradiol and phenol red, but not by the antiestrogen tamoxifen, in keeping with our previous results demonstrating estrogen induction of pS2 mRNA synthesis.
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PMID:Characterization of the estrogen-induced pS2 protein secreted by the human breast cancer cell line MCF-7. 366 45

The human pS2 gene, whose expression is restricted to breast cancer cells, and whose transcription is induced by oestrogen in the human breast cancer cell line MCF-7, has been cloned from both placental and MCF-7 cell DNA. The exon-intron organization has been established by electron microscopy using genomic DNA-cDNA or -mRNA hybrid duplexes and by sequencing the exons and exon-intron junctions. The overall organization within and around the pS2 gene is the same in placental and MCF-7 cell DNA and the exonic sequences are identical to those previously determined from the cDNA. The 5'-flanking region of the pS2 gene is also identical (with the exception of two base transitions) in the two tissues. Thus no gene rearrangement nor sequence modification has occurred in the pS2 gene of the malignant and polyploid MCF-7 cells. A TATA-box, a CAAT-box and a GC-rich motif are present in the 5'-flanking region of the pS2 gene, but the latter motif is unusually located between the TATA-box and the capsite. No significant homology could be detected between the 5' flanking sequences of the pS2 gene and those of other oestrogen-responsive genes from different species.
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PMID:Structure of the human oestrogen-responsive gene pS2. 382 34


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