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)

The human breast epithelial cell line, MCF-10A, derived from tissue from a woman undergoing a cutaneous mastectomy for fibrocystic breast disease, is negative for estrogen receptor expression, has undergone minimal genetic changes, retains many of the characteristics of normal breast epithelium and fails to exhibit growth in nude mice. When transfected with a functional copy of the estrogen receptor, both ER and MDM2 expression are negatively regulated by the presence of increasing concentrations of estradiol, as previously reported. We obtained the MCF-10A cell line from the American Type Culture Collection and confirmed that it was negative for ER expression. After approximately 20 passages under differing growth conditions, one subline was determined to be positive for ER expression. Growth of this ER-positive subline in phenol red-free media supplemented with charcoal-dextran stripped serum in the presence of nanomolar concentrations of estradiol failed to modulate ER and MDM2 expression, and induced expression of both pS2 and cathepsin D. Simultaneously with these observations, we observed that this subline, unlike the parent MCF-10A line, overexpressed P53 protein with a nuclear localization. Intermediate levels of the P53-inducible protein p21 WAF1/Cip1 were also detected in the ER-positive subline whereas levels of this protein in the parent subline were barely detectable, as measured by immunohistochemical methods. We conclude from these studies that ER expression and P53 alteration may constitute early steps in progression of malignant potential for breast cancer development.
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PMID:Spontaneous conversion to estrogen receptor expression by the human breast epithelial cell line, MCF-10A. 1020 82

Serrated adenoma of the colorectum was a newly proposed entity in 1990, characterized by epithelial neoplasia combining the architectural features of a hyperplastic (metaplastic) polyp with the cytological features of an adenoma. Its histogenesis and natural history still remain unclear. Forty-six serrated adenomas were obtained from 46 patients. The clinicopathological features were summarized. Paraffin-embedded blocks from 34 serrated adenomas were available for immunohistochemical studies using pS2, human gastric mucin, and p53 protein. Eighteen hyperplastic (metaplastic) polyps, 16 tubular adenomas, and 12 early-stage adenocarcinomas were randomly selected as control groups for immunohistochemical analysis. The patients' ages ranged from 32 to 86 (average 61.4) years. Males were more frequently affected than females. Serrated adenomas were predominantly present in the left-side of the colon and in the rectum (72 per cent). Their sizes ranged from 3 to 26 mm (average 9. 2mm). Six lesions (13 per cent) contained foci of high-grade dysplasia. These adenomas were significantly larger (12.7 mm) than those containing no high-grade dysplasia (8.6mm). pS2 and human gastric mucin were expressed significantly more frequently in both hyperplastic (metaplastic) polyps and serrated adenomas than in tubular adenomas or adenocarcinomas. p53-positive cells were present in 18 of the 29 pure serrated adenomas (62 per cent) and in one of the five areas of low-grade dysplasia in serrated adenomas with high-grade dysplasia (20 per cent), most of which revealed a sporadic distribution. Only five of the 29 serated adenomas with no high-grade dysplasia (17 per cent) were regarded as demonstrating p53 overexpression. On the other hand, three of the five areas of high-grade dysplasia in serrated adenomas (60 per cent) revealed diffuse positivity (3+) for p53 protein. The serrated adenoma, which possibly shows gastric differentiation, is considered to be an independent histological entity among the various phenotypes of colorectal adenomas. Serrated adenoma would seem to be a precursor of carcinoma, its potential for malignant transformation being similar to that of the traditional tubular adenoma. It would also seem that p53 is involved in the serrated adenoma-carcinoma sequence.
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PMID:'Serrated' adenoma of the colorectum, with reference to its gastric differentiation and its malignant potential. 1039 12

To evaluate the prognostic relevance of Ki-67 and topoisomerase IIalpha expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki-S11 (Ki-67) and Ki-S4 (topoisomerase IIalpha). pS2, c-erbB2, and p53 were additionally considered as prognostic variables. The median follow-up time was 149 months. Eight-hundred-and-sixty-three tumors reacted with Ki-S11 and Ki-S4; the labeling indices of the two antigens were closely associated (r = 0.93). Both correlated positively with the tumor size, c-erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki-S11 and Ki-S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis-free survival (p < 0.00001). Estrogen receptor status, p53, and c-erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki-S4 score >25% (p < 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki-S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki-S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIalpha expression as assessed by monoclonal antibody Ki-S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.
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PMID:Prognostic significance of Ki-67 and topoisomerase IIalpha expression in infiltrating ductal carcinoma of the breast. A multivariate analysis of 863 cases. 1047 80

This study was performed to evaluate the significance of pS2 and MUC1 expressions in ulcerative colitis (UC)-associated colorectal neoplasias. Tissues were collected from 6 patients with UC-associated colorectal neoplasias treated surgically. Specimens were 13 adenocarcinomas, 40 dysplasias (20 high-grade dysplasias, 20 low-grade dysplasias), and 60 normal mucosae. Tissues were also collected from patients without UC treated surgically or endoscopically. pS2, p53, and MUC1 expressions were examined immunohistochemically and compared. The K-ras codon 12 mutation was investigated by single-strand conformation polymorphism analysis. In patients with UC, the incidence of pS2 expression was significantly higher (p<0.01) in adenocarcinomas than it was in dysplasias, and no pS2 expression was seen in normal mucosae. p53 overexpression was detected in 50% (10/20) even in low-grade dysplasias. MUC1 expression was seen only in invasive carcinomas, but it was seen in 100% of cases (3/3). K-ras gene mutations were detected in 2 (20%) of 10 carcinomas. In low and high-grade dysplasias, the incidences of pS2 expression were significantly (p<0.01) lower than the incidences of p53 overexpression, however, in UC-associated carcinomas there was no significant difference; pS2 expression and p53 overexpression were detected in 13 of 13 (100%) cases and in 12 of 13 (92%) cases, respectively. These results suggest that p53 overexpression may be a diagnostic marker of neoplasia, and that pS2 expression may be a diagnostic marker of colorectal carcinoma in case of UC.
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PMID:pS2 expression as a possible diagnostic marker of colorectal carcinoma in ulcerative colitis. 1067 63

One hundred and seventy patients received breast-conserving therapy in the Second Department of Surgery, Gunma University School of Medicine. Six (3.5%) out of the 170 patients showed breast recurrence. We investigated the breast recurrent cases clinicopathologically. The age at the initial operation ranged from 38 to 78 (mean 57) years. One patient was clinical stage I and the others were clinical stage II. Surgical margin at the initial operation was negative in two patients and positive in four. Histological type was invasive ductal cancer in all cases. Three patients had lymph node involvement. The interval from the initial operation to breast recurrence ranged from 19 to 68 months. Five cases were nodular type and one was diffuse type of breast recurrence. Histological type of breast recurrence was the same as the initial one. We performed salvage surgery for all breast recurrent patients, mastectomy for four patients and local resection for two. One patient who showed diffuse type of recurrence could not be controlled with any surgical treatment, and later died of breast cancer. We investigated the expression of estrogen receptor, progesterone receptor, pS2, c-erbB-2 and p53 on both initial and recurrent specimens of the six patients. The expression of each protein on the recurrent specimens was the same as the initial one. We conclude that breast recurrence after breast-conserving therapy has its origin in the residue of cancer cells at the initial operation, even if surgical margins are histopathologically negative.
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PMID:Immunohistochemical study on primary and recurrent tumors in patients with local recurrence in the conserved breast. 1067 74

A 70-year-old woman underwent right hemicolectomy and six carcinomas were recognized in the resected colon. These carcinomas were considered to be of a cell lineage common to serrated adenoma (SA) and hyperplastic (metaplastic) polyp (H/MP), because of the occurrence of multiple SAs and H/MPs around the carcinomas, as well as the co-existence of SA and H/MP areas within the carcinomas. These carcinomas had the following common histological and immunohistochemical features: a serrated structure resembling SA; a lace-like structure; infiltrative growth within the muscularis propria, with dedifferentiation at the invasive front; and immunohistochemical expression of pS2 and human gastric mucin. Based on these features, a new subtype of carcinoma is proposed, with a cell lineage common to SA and H/MP. It would also seem that p53 is involved in the serrated adenoma-carcinoma sequence.
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PMID:Multiple 'serrated adenocarcinomas' of the colon with a cell lineage common to metaplastic polyp and serrated adenoma. Case report of a new subtype of colonic adenocarcinoma with gastric differentiation. 1069 93

Our aim was to compare the occurrence and prognostic significance over 14-20 years of immunocytochemically detected S100A4 and other tumour variables in primary tumours from 349 patients with operable breast cancer. For a cut-off of 1% staining of the malignant cells, the antibody to S100A4 stains positively 56% of the carcinomas. There was a significant association of staining for S100A4 with tumours fixed to the chest wall, staining for c-erbB-2, c-erbB-3, pS2, cathepsin D and, inversely, at borderline levels with staining for estrogen receptor. Using Wilcoxon statistics in univariate analyses, staining for S100A4, nodal status, tumour class, histological grade and staining for c-erbB-2, p53 were associated negatively and staining for estrogen receptor, progesterone receptor were associated positively with patient survival times. The survival times of patients with S100A4-negative carcinomas with or without one of the other tumour variables showed no significant differences, whilst those of patients with S100A4-positive carcinomas showed significant differences in a negative or a positive way. Multivariate regression analysis for 137 patients showed that staining for S100A4 is most highly correlated with patient deaths, but involved lymph nodes, fixed tumours, high histological grade and staining for progesterone receptor were also significant independent prognostic variables. Our results suggest that in this set of patients, the tumour variable most tightly correlated with patient death is S100A4.
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PMID:Comparison of the metastasis-inducing protein S100A4 (p9ka) with other prognostic markers in human breast cancer. 1075

The trefoil peptide family is comprised of three small peptides (designated pS2, SP, and ITF) exhibiting a unique motif of three intrachain loops formed by disulfide bonds. These highly protease-resistant peptides are secreted onto the mucosal surface by goblet cells or their equivalents. Most importantly, these factors protect epithelium from injury and promote repair through restitution after injury has occurred. Targeted deletion of the gene encoding ITF results in exquisite sensitivity to colonic injury by standard agents (e.g., dextran sodium sulfate) due to an inability to repair the epithelium. Studies have led to insight into the intracellular responses to trefoil peptides, including ras-dependent MAP kinase activation and activation of epidermal growth factor receptor. Among other effects, activation of these pathways is associated with redistribution of E-cadherin from the cell surface to intracellular domains, where it is complexed with catenins, and phosphorylation of akt, inactivating this kinase associated with apoptosis. In addition, trefoil peptides appear to block both p53 dependent and p53 independent apoptosis through pathways associated with activation of EGFR and P13 kinase. These observations suggest that trefoil peptides elicit a coordinated cellular response enabling cell migration without triggering the programmed cell death response usually precipitated by cell detachment from a stationary anchored state.
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PMID:Mechanisms of regulatory peptide action in the gastrointestinal tract: trefoil peptides. 1077 22

An accumulation of multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, cell adhesion molecules, and the growth factor/receptor system is involved in the course of multistep conversion of normal epithelial cells to clinical gastric cancer. Some of them differ depending on the histological type, well-differentiated (intestinal) and poorly differentiated (diffuse) types, suggesting the presence of two distinct genetic pathways. Genetic instability, chromosomal instability (telomere reduction), and immortality (activation of telomerase and expression of telomerase reverse transcriptase: TERT) participate in the initial step of stomach carcinogenesis. Because TERT protein expression precedes the telomerase activities in precancerous lesions, TERT expression may be a prerequisite for telomerase activation. The cyclin E gene is amplified in 15%-20% of gastric cancer. Reduced expression of a cyclin-dependent kinase (CDK) inhibitor, p27Kip1, is frequently found in gastric cancer associated with high grade malignancy. E2F-1, an important downstream target of cyclins/CDKs, is overexpressed in about 40% of gastric carcinomas, whereas gene amplification of E2F-1 rarely occurs. Loss of heterozygosity (LOH) of p73, the p53-related new tumor suppressor gene, preferentially occurs in well-differentiated adenocarcinomas of foveolar type expressing pS2, a gastric-specific trefoil factor, indicating the importance of p73 LOH in the genesis.
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PMID:Genetic and epigenetic alterations in multistep carcinogenesis of the stomach. 1077 29

Tamoxifen is one of the most effective treatments for breast cancer. Standard practice is to select patients who are likely to respond to this therapy through the evaluation of estrogen receptor (ER) and progesterone receptor (PR) in the primary tumor tissue. Over the past 25 yr that physicians have been using ER determination to guide tamoxifen use, numerous studies have demonstrated that this molecular marker is useful in predicting benefit from tamoxifen. ER has been analyzed for many years using ligand-binding assays. However, current practice involves the use of immunohistochemical-based assays to detect ERalpha Immunohistochemistry (IHC) has several advantages. For example, IHC evaluates tumor cell heterogeneity, can be used to study small samples, is less expensive, and allows direct correlation with multiple histopathological tumor features and other molecular markers. PR, an estrogen-responsive protein, can also be useful in predicting response to tamoxifen in specific clinical situations. In recent years, several other markers of tamoxifen response have been examined, including: pS2 (another estrogen-regulated protein), heat-shock proteins 27 and 70, bcl-2 protein, c-erbB-2 (HER-2/neu) oncoprotein, and mutated p53 tumor suppressor protein. In this article, we present an analysis of the data on these new molecular markers. Overall, from numerous studies, the data indicate that in addition to ERalpha bcl-2 is a potential candidate to help further improve our ability to predict response to tamoxifen. ER and bcl-2 are the most useful molecular markers to better identify breast cancer patients who will respond to tamoxifen and who will have prolonged survival.
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PMID:Molecular markers for predicting response to tamoxifen in breast cancer patients. 1105 Oct 41


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