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)

Approximately 50% of human breast tumors secrete a small cysteine-rich protein called pS2. In the human breast cancer cell line MCF-7, expression of the pS2 protein is strongly induced by estrogen, and cloning and sequence analysis of the pS2 gene has revealed an "estrogen responsive element" in the gene's 5'-flanking region. The results of immunohistochemical assays and radioimmunoassays on breast cancer biopsies indicate that the pS2 protein is a marker for hormone-dependent breast tumors and that its expression is associated with longer overall, and disease-free, survival. The pS2 protein is also expressed in normal stomach mucosa and in regenerative tissues in ulcerative diseases of the gastrointestinal tract. Its physiological function is unknown.
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PMID:The pS2 gene, mRNA, and protein: a potential marker for human breast cancer. 222 88

The pS2 gene encodes for a small cysteine-rich protein, and was originally found by differential screening of a cDNA library from the human breast carcinoma cell line, MCF-7. The presence of pS2 is closely correlated with oestrogen dependence in breast carcinomas. While the function of pS2 is unknown, pS2 protein has been shown to be homologous with the gastrointestinal peptide hormone pancreatic spasmolytic polypeptide (PSP) and its human counterpart hSP, in which a 5-cysteine domain is tandemly repeated. The 5' flanking region of the pS2 gene contains an enhancer region responsive to oestrogens and to epidermal growth factor (EGF/URO). We now report that pS2 and hSP expression occurs in a wide range of endodermally-derived tissues, including the duodenum, the pancreas, and in a recently defined cell lineage associated with chronic gastrointestinal ulceration. In each case, this expression was associated with secretion of immunoreactive EGF/URO. We further show that the co-expression of pS2 and hSP in gastric surface epithelial cells is also associated with the secretion of EGF/URO in the subjacent mucous neck cells. Our results indicate that local EGF/URO secretion induces pS2 and hSP in adjacent cells, and that these molecules are then available to participate in pathophysiological responses. The finding of similar patterns of EGF/URO, hSP and pS2 expression in association with chronic damage suggests that this is a fundamental response in the healing of these tissues.
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PMID:Epidermal growth factor (EGF/URO) induces expression of regulatory peptides in damaged human gastrointestinal tissues. 229 Jan 13

Approximately 50% of human breast tumors secrete a small cysteine-rich protein, pS2, of unknown function. pS2 protein was recently found to be homologous to a porcine protein with hormonogastric activity, pancreatic spasmolytic polypeptide (PSP), in which the 5-cysteine domain present in pS2 is tandemly duplicated. We have characterized cDNA species encoding PSP and its human and mouse counterparts, hSP and mSP. We show that hSP and pS2 are separately encoded in the genome, and that the two proteins are co-expressed in normal stomach epithelium. However, expression of hSP was not detected in breast tumors. Computer analysis revealed that the pattern of conserved cysteine residues in hSP and pS2, the P domain, is present at the N termini of two other mammalian proteins, intestinal sucrase-isomaltase and lysosomal alpha-glucosidase.
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PMID:hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma. 230 34

Human intestinal trefoil factor (hITF) is a small cysteine-rich protein expressed in the gastrointestinal (GI) tract. Its sequence is related to that of other trefoil peptides including the pNR-2/pS2 protein, which is regulated by oestrogen in breast cancer. This study was designed to investigate whether hITF is expressed in human carcinoma cells. cDNA was obtained by reverse transcription-polymerase chain reaction (RT-PCR) of gastric mucosal RNA and sequenced, establishing that this mRNA is expressed in the stomach. Expression of hITF was detected in a proportion of cell lines derived from malignancies of the GI tract, in hepatocellular carcinoma cells, and at highest levels in a small cell lung carcinoma cell line. Amongst breast cancer cell lines, it was expressed in all the oestrogen-responsive but in none of the oestrogen-nonresponsive breast cancer cell lines. The possibility that hITF expression in breast cells is controlled by oestradiol was then tested. Oestradiol treatment increased hITF expression between three- and ten-fold in the oestrogen-responsive breast cancer cell lines, demonstrating that, like pNR-2/pS2, hITF is regulated by oestrogen in breast cancer cells. Tamoxifen inhibited the induction of hITF expression by oestradiol but tamoxifen alone was a partial oestrogen agonist for hITF expression. These results show that hITF is expressed, sometimes ectopically, in several human malignancies, which suggests that trefoil peptides may have a more general role in tumourigenesis than hitherto appreciated. That the expression of hITF is regulated by oestrogen in breast cancer cells suggests that hITF expression may provide a novel marker for oestrogen responsiveness in breast cancer.
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PMID:Expression of human intestinal trefoil factor in malignant cells and its regulation by oestrogen in breast cancer cells. 930 61

The evaluation of prognostic factors for breast cancers is important for therapeutic decisions both at the time of surgery and during postoperative surveillance. Cathepsin-D (cath-D) is an estrogen inducible aspartyl protease. Studies have demonstrated two biological activities, at an acidic PH, of the protein: a mitogenic and a proteolytic activity; both the growth promoting activity and the extracellular proteolytic activity suggest that cathepsin D (cath-D) may have prognostic significance in breast cancer. Measurement of cath-D in breast tissue, in fact, is highly significant in predicting recurrence as well as disease free interval and overall survival. The pS2 is a small cysteine-rich protein specifically expressed under estrogen transcriptional control. Expression of the pS2 protein in breast carcinoma is a useful guide to prognosis and response to tamoxifen: appropriate adjuvant therapy can be selected on the pS2 status of the tumor; patients with pS2 expression had better overall survival and a longer survival time after the first recurrence than those without pS2 expression. For these reasons, these two new prognostic markers could be suggested as habit factors in breast cancer.
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PMID:Prognostic significance of the estrogen-regulated proteins, cathepsin-D and pS2, in breast cancer. 956 Oct 19

TFF1 is a cysteine-rich protein that forms a characteristic trefoil domain through disulfide bonds, which render it resistant to vigorous conditions and it involves in maintaining the integrity of the gastric mucosa. Decreased expression of TFF1 gene plays a role in the development of gastric cancer. We examined the association between the promoter polymorphisms of the TFF1 gene and the risk of development of gastric cancer, in a case-control study including 199 controls and 141 patients with gastric cancer. Assessment of single nucleotide polymorphisms in the promoter region of the TFF1 gene was performed by sequencing and polymerase chain reaction-based restriction fragment length polymorphism. We found a statistically significant increased risk of gastric cancer associated with -394 TT genotypes (OR=8.78, CI=2.85-27.05, p<0.001) and CT (OR=1.64, CI=1.04-2.60, p=0.033). This single nucleotide polymorphism occurs naturally in an estrogen response element. According to induction of the TFF1 gene by estrogen, it is possible that the substitution of C to T results in a decreased estrogen receptor binding affinity to the estrogen response element and in turn it decreases the expression of the TFF1 gene that may be involved in development of gastric cancer over a lifetime.
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PMID:Polymorphism of estrogen response element in TFF1 gene promoter is associated with an increased susceptibility to gastric cancer. 2209 77