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

This study was undertaken to relate the expression of the proliferating cell nuclear antigen (PCNA), a proliferation marker of putative prognostic significance, to some more established prognostic factors in a series of 60 consecutive breast cancer surgical specimens. PCNA was detected by the PC10 monoclonal antibody (MAb) using an immunohistochemical method and PCNA immunostaining was estimated on a semiquantitative basis, a cut-off value of 50% of positively stained tumour cells discriminating between the high (> 50%) and low (< 50%) PCNA grade. The PCNA grade did not correlate with tumour size and axillary node status. However, a high PCNA grade tended to be associated with a poor histological grade and there was an inverse relationship with oestrogen-receptor status, as determined by means of the immuno-histochemical staining for the oestrogen-induced pS2 protein. These conflicting results suggest that the possible prognostic usefulness of PCNA immunostaining, as a measure of cell proliferation rate, in breast cancer is yet to be demonstrated and can be validated only by direct relation to survival data.
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PMID:Cell proliferation in breast carcinoma assessed by a PCNA grading system and its relation to other prognostic variables. 790 63

In the present study, pS2 protein expression in pulmonary adenocarcinoma was investigated on paraffin-embedded sections obtained from 170 patients. 28 (16%) patients showed varying degrees of pS2 protein expression in the cytoplasm of tumour cells, as detected by immunohistochemical staining with anti-pS2 protein antibody. There was a significant association between pS2 protein expression and larger tumour size, and the acinar or bronchiolo-alveolar subtype. However, no significant correlations between pS2 protein status and the other clinicopathological factors, i.e. T-factor, N-factor, stage and histological differentiation, were shown. In contrast to breast cancer, patients with pS2-positive pulmonary adenocarcinomas had a significantly worse prognosis than those with pS2-negative pulmonary adenocarcinomas; this was true for stage I patients, as well as for all patients. Multivariate analysis showed that pS2 protein expression was a discriminating variable in overall survival. These findings suggest that pS2 protein status is a possible prognostic indicator in pulmonary adenocarcinoma.
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PMID:Prognostic significance of pS2 protein expression in pulmonary adenocarcinoma. 791 39

Proliferation of the human breast tumor cell lines T47D and MCF7 was stimulated by high concentrations (10(-6) M) of the synthetic progestins gestodene and 3-ketodesogestrel, but not by Org2058, comparable to the stimulation by low dosages of estradiol (10(-10) M). At physiological concentrations of the progestins (10(-10) M) only T47D cells responded. Using specific antihormones it was shown that the effect at pharmacological dosages is mediated by a crossreaction of these compounds with the estrogen receptor (ER), while the stimulation of T47D cells at physiological concentrations seems progesterone receptor (PR) mediated. This was further substantiated using transient transfection assays with ER- and PR-inducible reporter constructs and mRNA induction of the ER- and PR-target genes pS2 and fatty acid synthetase, respectively. Using a whole cell ligand binding assay, 20-fold higher amounts of PR were measured in T47D compared to MCF7 cells. This was in line with a much higher PR-dependent transactivation in T47D cells and suggests that the level of transcriptionally active PR is a major determinant for the response to physiological concentrations of progestins in human breast cancer cells.
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PMID:Synthetic progestins induce proliferation of breast tumor cell lines via the progesterone or estrogen receptor. 792 73

Expression of the hormone-regulated genes, pS2, prolactin-inducible protein (PIP) and fatty acid synthetase (FAS), was investigated by Northern blotting in primary breast carcinoma, metastatic breast cancer in axillary lymph nodes, in uninvolved breast tissue from mastectomies and in normal lymph nodes. There were considerable differences in expression of the genes between the tissues. The proportion of tissues containing PIP-mRNA decreased from uninvolved breast tissue to primary breast carcinoma to metastatic carcinoma. The reverse applied to FAS-mRNA which was found more often in metastatic cancer than in primary cancer, and least frequently in uninvolved breast tissue. Yet another pattern was observed for pS2 expression. The highest proportion of tissues demonstrating gene expression was found in primary breast cancer with both metastatic tumor and uninvolved breast tissue expressing the gene less frequently. pS2-mRNA and PIP-mRNA could only rarely be detected in trace amounts in normal lymph nodes. In contrast, FAS-mRNA was present in about one third of normal lymph nodes. Only pS2-mRNA showed an association with estrogen and progesterone receptor status.
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PMID:Hormone-regulated genes (pS2, PIP, FAS) in breast cancer and nontumoral mammary tissue. 794 16

Treatment of astrocytes with interleukin (IL)-6, -7 and tumor necrosis factor (TNF)-alpha produced a marked increase in the expression of the pS2 gene, an estrogen-inducible gene originally identified in the human breast cancer cell line MCF-7. The effect of IL-6 and TNF-alpha was completely inhibited by the addition of anti-IL-6 monoclonal antibody and anti-TNF-alpha monoclonal antibody, respectively. During the treatment with IL-6 and TNF-alpha, neither increase in thymidine incorporation nor morphological change was observed. Inhibition of protein synthesis by cycloheximide and inhibition of RNA synthesis by actinomycin D abrogated the stimulatory effect on pS2 mRNA expression of IL-6 and TNF-alpha, suggesting that new protein synthesis as well as new RNA synthesis was required for their action. These results suggest that brain injury trigger pS2 gene expression in astrocytes through the induction of cytokines.
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PMID:Cytokine regulation of PS2 gene expression in mouse astrocytes. 795 Oct 69

Fine-needle aspirates from 52 breast cancers in 50 patients over 70 years of age were immunocytochemically stained for pS2 protein. All patients were treated with tamoxifen 40 mg/day and followed up at intervals of 2 months. The size of the tumour was serially assessed with calipers and portable ultrasonography. Change in tumour size was confirmed mammographically. Clinical monitoring was performed bind of the pS2 status. Twenty-five tumours were pS2 positive, of which 23 showed a significant response; ten went into complete remission (mean time to complete remission 6.8 (range 2-14) months) and 13 demonstrated partial remission (mean follow-up 8.9 (range 6-19) months). Two tumours remained static. Twenty-seven tumours were pS2 negative and none of these responded to tamoxifen; six remained static (mean follow-up 11.5 (range 6-14) months) and 21 progressed (mean time to progression 7.0 (range 3-14) months) (P < 0.001). Immunocytochemical assessment of fine-needle aspirates from elderly women with breast cancer accurately predicts a worthwhile response to tamoxifen.
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PMID:Immunocytochemical staining of pS2 protein in fine-needle aspirate from breast cancer is an accurate guide to response to tamoxifen in patients aged over 70 years. 795 46

pS2 is an estrogen-induced mRNA species that was originally identified in the breast cancer cell line MCF-7. Exposure of the cells to basic fibroblast growth factor (bFGF) at the concentration of 10-100 ng/ml for 48-72 h resulted in a marked increase in the concentration of pS2 protein in the medium. The polymerase chain reaction with reverse transcriptase revealed that bFGF increased the amount of intracellular pS2 mRNA: immunocytochemical studies showed that exposure to the factor increased the amount of intracellular pS2 protein. Simultaneous addition of cycloheximide with bFGF completely abolished induction of pS2 protein, although it did not affect the induction of pS2 mRNA. Actinomycin D did not affect the stimulatory effect of bFGF on synthesis/secretion of pS2 protein. bFGF effectively abolished decay of the pS2 mRNA level caused by actinomycin D. These results suggest that the induction of the synthesis/secretion of pS2 protein by bFGF occurs at the post-transcriptional level, most probably due to the stabilization of pS2 mRNA. Another finding, that bFGF and estradiol have a synergistic effect on induction of pS2 protein, suggests the possibility that these two inducers act by a different but partly overlapping mechanism.
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PMID:Effect of basic fibroblast growth factor on synthesis/secretion of pS2 protein by human breast cancer cells (MCF-7). 795 94

All-trans retinoic acid (tRA) inhibits growth of estrogen receptor-positive (ER+) breast cancer cells in vitro, and a variety of retinoids inhibit development of breast cancer in animal models. 9-cis retinoic acid (9-cis RA) is a naturally occurring high affinity ligand for the retinoid X receptors, as well as the retinoic acid receptors (RARs). Whether 9-cis RA has a different spectrum of biological activity from tRA, which only binds RARs with high affinity, is largely unknown. We studied the effects of 9-cis RA on growth and gene expression in ER+ and ER- human breast cancer cells. 9-cis RA inhibited the growth in monolayer culture of several ER+, but not ER-, cell lines in a dose-dependent manner. Growth inhibition and morphological changes by 9-cis RA were similar to those of tRA, suggesting that the ability to bind both RAR and retinoid X receptors did not significantly augment growth inhibition or confer sensitivity to tRA-resistant lines. MCF-7 cells exposed to 9-cis RA showed a dose-dependent accumulation in G1. Northern analyses showed that RAR-alpha and RAR-beta were not significantly regulated, while RAR-gamma was up-regulated and retinoid X receptor alpha was down-regulated by 9-cis RA. Since interactions between tRA and ER-dependent transcription have recently been reported, we investigated whether these retinoids regulate expression of ER itself or estrogen-responsive genes. Both 9-cis RA and tRA induce down-regulation of ER mRNA and protein in MCF-7 cells. 9-cis RA down-regulates expression of the estrogen-responsive genes PR and pS2 in MCF-7 cells as reported previously for tRA. In several ER-positive subclones, we found that the degree of ER expression and regulation, but not always estrogen-sensitivity, correlates with the growth-inhibitory effects of 9-cis RA. Further, in an ER-, retinoid-unresponsive breast cancer cell line, induced ER expression confers responsiveness to retinoid growth inhibition. These data, combined with reports of additive growth inhibition of tRA and tamoxifen in vitro, suggest that 9-cis RA might augment the ability of tamoxifen to inhibit growth of ER+ breast cancer cells in vivo.
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PMID:9-Cis retinoic acid inhibits growth of breast cancer cells and down-regulates estrogen receptor RNA and protein. 798 55

A sensitive two-site enzyme immunoassay (EIA) system was established for human pS2 protein, a small estrogen-inducible secretory protein of unknown function originally identified in MCF-7 human breast cancer cells. Our EIA system is based on the sandwiching of antigen between anti-recombinant (r) pS2 antibody IgG coated on a polystyrene plate and biotinylated anti-rpS2 antibody IgG. The amount of pS2 protein was quantified by measurement of the bound enzyme activity of subsequently added streptavidin-linked beta-D-galactosidase (beta-D-galactosidase, EC 3.2.1.23). pS2 protein purified from MCF-7 culture supernatants was detectable at a concentration as low as 3 pg/ml (corresponding to 60 fg/well). This EIA system revealed that the amount of pS2-like immunoreactivity (LI) in human urine was 13.6 ng/mg creatinine (median, n = 416) and that there was no correlation between the pS2-LI concentration in urine and sex or aging. pS2-LI levels in plasma and sera of the normal subjects were 392 pg/ml (median, n = 14) and 494 pg/ml (median, n = 12), respectively. The serum level of the patients with breast cancer (528 pg/ml; median, n = 67) was not statistically different from that of normal subjects, although high levels of pS2 protein in breast cancer tissues had been reported.
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PMID:Estimation of pS2 protein level in human body fluids by a sensitive two-site enzyme immunoassay. 798 37

We evaluated the prognostic value of tissue polypeptide antigen (TPA), cathepsin D and pS2 in 267 patients operated for primary breast cancer. Cathepsin D, pS2 and cytosol TPA were independent of each other and of N, T, estrogen (ER) and progesterone (PgR) receptors. Cathepsin D was the best prognostic indicator for disease-free survival and pS2 for overall survival. The simultaneous evaluation of the three parameters was an effective discriminator between high and low risk patients in both N- and N+. Considering that cathepsin D, pS2 and cytosol TPA can be easily measured with reliable methods in small amounts of tissue, we conclude that they are a promising panel of biochemical parameters suitable for the assessment of the risk of relapse in patients with breast cancer.
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PMID:Biochemical parameters for prognostic evaluation in patients with breast cancer. 801 Jul 28


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