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)

We have introduced the human estrogen receptor (ER) gene into HeLa cells, a human adenocarcinoma cell line of uterine origin, by infection. The ER cDNA was inserted into a retroviral vector (pMV7-ER) which also contains the neomycin resistance gene to allow for selection of stable infected clones. Northern analysis showed exogenous ER expression in stable clones. The ER protein expressed was about 66 kDa, similar to native MCF-7 ER, and binds with high affinity to estrogen (E2). We have also observed that addition of E2 at 10(-8) M inhibits the growth of the I-1 clone which expresses high levels of the ER (223 fmol/mg cytosol protein). The inhibitory effects of E2 directly correlate with the quantity of ER in the cells. E2-induced gene expression analysis showed that pS2 and progesterone receptor (PgR), genes induced in MCF-7 cells by E2, are not induced in the ER+ HeLa clones. However, c-myc expression was found to be decreased and may be responsible for the observed growth inhibition by E2.
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PMID:Stable expression of the human estrogen receptor in HeLa cells by infection: effect of estrogen on cell proliferation and c-myc expression. 168 89

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.
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PMID:Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. 189 37

NH2-terminal amino acid sequence of the pS2 protein produced and secreted by human gastric cancer cells, MKN-45, was determined to be identical to that of MCF-7 cells. A clone encoding pS2 protein was isolated from the cDNA library constructed from MKN-45 cells. The nucleotide sequence was identical to that of pS2 cDNA previously isolated from human breast cancer cells, MCF-7, except for one nucleotide in the 3' untranslated region. Thus, in this cell line, the pS2 gene product is translated and secreted as in MCF-7 cells. RNA blot hybridization analysis revealed that pS2 gene was expressed well in two (MKN-45 and KATO-III; derived from poorly differentiated adenocarcinoma) but not in three cell lines (MKN-1, MKN-28 and MKN-74; from well differentiated adenocarcinoma), suggesting that expression of the pS2 gene depends on the state of cell differentiation. These results suggest that pS2 is expressed in human gastric cancer cells in an estrogen-independent manner and is possibly associated with the malignant state of cells.
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PMID:Expression of the pS2 gene in human gastric cancer cells derived from poorly differentiated adenocarcinoma. 231 59

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

The breast cancer-associated protein pS2 is also present in many human gastrointestinal tumors. In contrast to breast carcinomas, gastrointestinal tumors do not express estrogen receptors, indicating that the expression of pS2 is not estrogen-dependent. The pS2 expression was analyzed in 14 adenosquamous tumors of the human gastrointestinal tract. The aim was to investigate if the cell type specific localization of pS2 was limited to the glandular part. The data clearly confirm such a specific compartmentation of the pS2 expression, suggesting pS2 to be a secreted protein. Due to the specific expression, pS2 may become a new and useful diagnostic marker of adenocarcinoma.
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PMID:Expression of the breast cancer-associated protein pS2 in adenosquamous carcinomas of the gastrointestinal tract. 832 70

This study was aimed at assessing the significance of pS2 immunostaining in colorectal adenocarcinoma and adjacent tissue. Paraffin sections of 63 surgically resected colorectal adenocarcinomas were stained with a pS2 specific monoclonal antibody using the avidin-biotin complex immunoperoxidase technique. Several tumor sections also included adjacent nonneoplastic mucosa. Six tubular adenomas and five hyperplasic polyps found in the resected bowels were also examined. Focal staining for pS2 was seen in 32 tumors (51%). In all but one case, less than 10% of the tumor cells were stained. pS2 staining was more common in right-sided than in left-sided tumors (p < 0.05), and was more prevalent in Dukes C than combined Dukes A and B tumors (p < 0.05). No significant relationship was found between pS2 positivity and the degree of tumor differentiation, patients' sex, or outcome of the disease as judged by the development of recurrence or metastasis. Strong pS2 positivity was seen in hyperplastic polyps and in nonneoplastic mucosa adjacent to many tumors. Tubular adenomas were either negative or showed focal superficial staining. It is concluded that pS2 immunostaining in colorectal adenocarcinoma does not seem to have prognostic significance, but may reflect developmental differences between the right and left side of the colon. The presence of pS2 staining in adjacent nonneoplastic mucosa and in hyperplastic polyps suggests that the epithelium in these areas is of a regenerative or reactive nature.
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PMID:pS2 immunostaining of colorectal carcinoma. 841 90

pS2 is a 60 amino acid secretory polypeptide which belongs to a newly described family of trefoil-shaped growth factors. It is widely distributed throughout the gastrointestinal tract, particularly adjacent to damaged mucosa, and is also expressed by some epithelial tumours such as breast carcinoma. The aim of this study was to examine the expression of pS2 in pancreatic cancer. The presence of pS2 was analysed immunohistochemically using two antibodies, a polyclonal (pNR-2) and a monoclonal (pS2TM) in 42 cases of pancreatic adenocarcinoma and 10 cases of ampullary carcinoma. The findings were compared with chronic pancreatitis and normal pancreas. No immunostaining was seen in normal pancreas, with the exception of one area of ductular proliferation, and although 8/10 cases of chronic pancreatitis expressed pS2, it was focal and confined to the occasional duct. In contrast, a significant proportion of malignant cells in 23/42 (55%) of pancreatic adenocarcinoma and 8/10 (80%) of ampullary tumours expressed immunoreactive pS2. The finding of pS2 expression in more than 50% of pancreatic and ampullary carcinomas in contrast to the findings seen in chronic pancreatitis and normal pancreas suggests that pS2 may play an important role in the growth of these highly malignant tumours.
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PMID:Immunolocalization of pS2, a putative growth factor, in pancreatic carcinoma. 852 4

We measured pS2 protein in the serum of patients with adenocarcinoma and non-adenocarcinoma types of lung cancer, non-cancerous lung lesions, and the control sera. Although the serum pS2 protein level in patients with lung adenocarcinoma was significantly higher than that in patients with other diseases, as well in control samples, it had little clinical value as a screening tumor marker because the levels in control samples showed a wide range of variation. However, analysis according to the histological subtype of lung adenocarcinoma, ordinary and bronchioloalveolar, revealed a high serum level of pS2 protein in several patients with advanced stage disease in the former, and mucus-producing goblet cell subtypes in the latter, which showed strong pS2 protein expression in tissues, whose serum levels diminished to the control level after resection. Thus, the serum levels of pS2 protein may be a useful marker of tumor burden in selected patients with lung adenocarcinoma.
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PMID:Estimation of serum level of pS2 protein in patients with lung adenocarcinoma. 869 68

We describe the first model system employing human pS2 gene transfer and expression in a non-pS2-expressing cell line, mouse mammary adenocarcinoma 410.4, in order to analyse the potential effect of human trefoil peptide pS2 in glandular epithelium. Two selected clones, AA4 and AD4, were established and shown to have incorporated the pS2 cDNA sequence into the genome, express pS2 containing transcript and produce the pS2 peptide. When grown in 3-D collagen gels both transfectants show striking morphological changes compared to the vector control clone (VA5). VA5 forms large cohesive spherical aggregates with rare coarse spicular outgrowths, accompanied by prominent hyalinised extracellular matrix deposition. pS2 transfectants form poorly cohesive, stellate colonies with very little or no matrix deposition, radiating long cords composed of single elongated cells, an effect previously observed in other cell lines with hepatocyte growth factor. pS2 transfection had no demonstrable effect on proliferation and this is not a morphogenetic phenomenon, as tubulogenesis is not seen. Motility assays suggest that the pS2 'dispersant' effect in collagen gels is due to an increase in cell motility. There were no measurable alterations in either E-cadherin expression or E-cadherin-dependent cell-cell aggregation. pS2 may play a role in maintenance and restitution of mucosal integrity by accelerating migration/dispersion.
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PMID:pS2 transfection of murine adenocarcinoma cell line 410.4 enhances dispersed growth pattern in a 3-D collagen gel. 883 91

Regulation of two genes involved in tumor invasion, the matrix metalloproteinase (MMP)-1 and the tissue inhibitor of MMP (TIMP)-1, by activators of protein kinase C (PKC) or protein kinase A (PKA) was studied in MCF-7 mammary adenocarcinoma cells. The basal mRNA expression was undetectable for MMP-1 and low for TIMP-1. Treatment of MCF-7 cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (100 nM) was associated with a high expression of MMP-1 mRNA, as well as an induction of the level of TIMP-1 mRNA (5- to 10-fold). In the presence of actinomycin D (AMD, 4.0 microM), an inhibitor of transcription, these stimulatory effects of TPA were abolished. Similar responses were observed when protein synthesis was inhibited by cycloheximide (CHX, 50 microM). In the presence of the cyclic AMP (cAMP) analogue N6-benzoyl (N6-Bzl)-cAMP (500 microM), the MMP-1 mRNA was unaffected and still below the level of detection, whereas a non-significant increase (< 2-fold) in TIMP-1 mRNA was observed. The level of pS2 mRNA, of which the induction by TPA in MCF-7 cells is a primary transcriptional event, was up-regulated (10- to 15-fold) by TPA (100 nM), whereas a much weaker increase (2- to 3-fold) was observed by treatment with N6-Bzl-cAMP (500 microM). Again, these stimulatory effects were counteracted by AMD (4.0 microM) and CHX (50 microM). These data suggest that activation of PKC but not of PKA may induce transcription of MMP-1 and TIMP-1, possibly by the synthesis of transcription factor(s), in transformed cells of epithelial origin.
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PMID:Regulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in MCF-7 cells: comparison with regulatory mechanisms of pS2 expression. 887 12


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