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)

Previous articles have reported that the c-myb proto-oncogene was activated in various types of tumours of the hematopoietic system suggesting that this gene plays a role in the development of these malignancies. However no studies of the c-myb gene have as yet been performed in solid primary tumours. In the present study we have analysed in breast cancer the c-myb gene with the aim to determine its involvement in tumour progression. Expression of the c-myb oncogene was analysed from 169 carcinoma specimens obtained from untreated patients with non-inflammatory breast cancer (NBC) (112 patients) and inflammatory breast cancer (IBC) (57 patients). A 3.5 kb c-myb transcript band was detected in 108 (64%) tumours. c-myb expression was found to be associated with good prognostic factors (lowest histopathologic grade (P = 0.01), oestrogen and progesterone receptor status (P less than 10(-4)) and pS2 gene expression (P less than 10(-4)) and negatively correlated with breast cancers of poorer prognosis, namely IBC (P = 0.03) and NBC with multiple involved nodes (P = 0.15). Other genes (c-myc, c-erbB2, c-fos and epidermal growth factor receptor) were also studied. The c-myb gene expression was found to be inversely correlated (P less than 0.03) with only c-erbB2 overexpression in NBC. When data were analysed with a logistic regression model using a stepwise procedure, c-myb expression was found to be associated only with the oestrogen receptor status (P less than 10(-4)). In conclusion, our data indicate that analysis of c-myb expression in breast cancer could allow the characterization of a new class of oestrogen-dependent tumours.
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PMID:Strong association between c-myb and oestrogen-receptor expression in human breast cancer. 218 74

The expression of genes which may be involved in the regulation of human mammary epithelial cell growth [transforming growth factors alpha and beta] and tumorigenesis [c-myc, erbB2, epidermal growth factor receptor (EGFR), Ha-ras, pS2] has been compared in similarly cultured normal cell strains and tumor cell lines. We have found that the normal breast cells produce high levels of EGFR mRNA, which are translated into nearly 10(5) low affinity epidermal growth factor-binding molecules/cell. In the estrogen receptor-negative lines examined, the EGFR gene was expressed at levels comparable to those in the normal cells. In contrast, EGFR and transforming growth factor alpha mRNAs were reduced in estrogen receptor-positive tumor lines compared to estrogen receptor-negative lines and normal cells. Steady state mRNA levels for transforming growth factor beta, erbB2, c-myc, and Ha-ras in the normal cells were greater than or comparable to those in all of the breast tumor lines. Furthermore, in the absence of gene amplification, only one of the genes examined (i.e., pS2) was overexpressed in a subset of the tumor cells compared to their normal counterparts. Several reports by other investigators have described overexpression of some of these genes in breast biopsies and in tumor lines in studies lacking normal controls. Thus, our results, in which the same genes were not overexpressed compared to normal cells unless amplified, underscore the importance of including appropriate normal controls in studies aimed at defining aberrant patterns of gene expression in tumor cells.
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PMID:Expression of growth factors and oncogenes in normal and tumor-derived human mammary epithelial cells. 319 80

For quantificative determination of ERBB2 gene amplification in archival human carcinoma specimens we have developed a rapid, non-radioactive approach, which is based on the differential polymerase chain reaction (PCR) and fluorescent DNA technique. Sequences from the ERBB2 gene and from a single-copy reference gene were amplified simultaneously by PCR, in which one of each primer pair was fluorescently labelled. PCR products were separated by polyacrylamide gel electrophoresis in an automated DNA sequencer and directly quantified after laser activation and emission scanning using appropriate software. This fluorescent differential polymerase chain reaction (fd-PCR) method was used for quantificative determination of ERBB2 gene amplification in 195 formalin-fixed, paraffin-embedded breast carcinoma tissues. ERBB2 gene amplification was found in 52 (26%) of these tumors and correlated significantly with tumor size, absence of estrogen receptor (ER) and pS2 expression, but not with absence of progesterone receptor (PR) or presence of epidermal growth factor receptor (EGF-R) expression, lymph-node metastases or grading. In univariate analysis, ERBB2 gene amplification showed no significant correlation with clinical outcome, either in the whole population or in the subgroup defined by positive axillary lymph-node metastases. However, within the node-negative subgroup, patients with ERBB2 gene amplification had significantly decreased relapse-free survival and overall survival (p < 0.05). The fd-PCR assay is a valuable tool for determination of amplification of ERBB2 gene as well as further oncogenes. In this way, more detailed information about individual tumor biology may be acquired by a routine assay.
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PMID:ERBB2 gene amplification detected by fluorescent differential polymerase chain reaction in paraffin-embedded breast carcinoma tissues. 759 Dec 99

The authors immunohistochemically studied the expression of the estrogen receptor (ER), 27-kD heat shock protein (HSP27) and pS2 in 118 invasive primary human breast cancers. Positive nuclear staining of the ER was detected in 64% of the cases and was closely correlated with the biochemical assay (p < 0.0001). ER-positive tumors were significantly decreased with tumor size and stage (p < 0.001 each), but not with lymph node status. Positivity of the ER was correlated with the cytoplasmic expression of HSP27 (p < 0.005), pS2 (not significant) and HSP70 (not significant). ER negativity was significantly correlated with the expression of p53, epidermal growth factor receptor (EGFR) and c-erbB-2 (p < 0.05 each). Thus, it was concluded that ER-positive breast carcinomas, relatively small in size, preferentially expressed HSP27, HSP70 and pS2 and that ER-negative tumors, relatively large in size, were predisposed to express p53, EGFR and c-erbB-2.
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PMID:Immunohistochemical detection of estrogen receptor in invasive human breast cancer: correlation with heat shock proteins, pS2 and oncogene products. 763 53

The trefoil peptides pS2 and human spasmolytic peptide are putative growth factors, particularly associated with mucus-producing cells of the gastrointestinal tract including those of the stomach. The receptor for transforming growth factor alpha (TGF alpha) takes its name from one of its alternative ligands, epidermal growth factor, and is called the epidermal growth factor receptor. Although there is immunoreactive epidermal growth factor in the stomach, it is TGF alpha and the epidermal growth factor receptor that are abundant. Immunolabelling at electron microscope level allows for subcellular localisation of antigens; pS2 and human spasmolytic peptide co-localise to cytomembranes, including the Golgi apparatus, and thecae of surface/pit mucous cells. TGF alpha is abundant on the membranes of tubulovesicles of parietal cells and is also present in chief cells: in mucous producing cells it can be detected but not in association with mucous. The distribution of the epidermal growth factor receptor mimics that of TGF alpha but with preferential clustering on the basolateral membranes of gastric cells. The trefoil peptides are associated with healing and probably act, together with mucus, to protect the gastric mucosa and maintain a viable environment. TGF alpha, transduced via the epidermal growth factor receptor, inhibits gastric acid secretion, thus aids the trefoils in the maintenance of a gastric microenvironment conducive to healing after damage. TGF alpha, however, is also a potent mitogen; while this property plays a vital part in repairing mucosal defects, if this peptide or indeed its receptor are overexpressed, the result can be neoplasia.
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PMID:Subcellular distribution of peptides associated with gastric mucosal healing and neoplasia. 767 Jan 62

A series of 201 bladder cancer biopsy specimens was analysed immunohistochemically for the expression of pS2 protein. Altogether, 61 per cent of the tumours were pS2-negative; in 16 per cent less than 1 per cent and in 23 per cent of cases more than 1 per cent of cells were pS2-positive. Normal transitional epithelium was negative for pS2. The fraction of positive cells was higher in poorly differentiated non-papillary tumours and in invasive tumours with pelvic lymph-node (P = 0.05) and distant metastasis (P = 0.10). pS2 expression was not related to sex, while patients aged 60-70 years had low fractions of pS2-positive cells (P = 0.03). DNA ploidy, S-phase fraction, mitotic index, morphometric nuclear features, and expression of c-erbB-2, p53, and epidermal growth factor receptor were independent of expression of pS2. Tumours expressing pS2 in over 10 per cent of cells had a lower survival probability (P = 0.0486). The results show that pS2 is expressed in 40 per cent of transitional cell bladder tumours, but that this marker has no clinical significance over established prognostic factors.
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PMID:Expression of pS2 protein in transitional cell bladder tumours. 796 92

Expression of the erbB-2 oncogene in breast cancer patients correlates with poor prognosis and failure of hormonal therapy. In this study, the effects of a putative erbB/HER ligand, gp30, on estrogen receptor (ER) concentration and activity was investigated in the estrogen receptor positive human breast cancer cells, BT474 and MCF-7, which express either high or low levels of erbB-2 and erbB-4, respectively. Treatment of cells with gp30 resulted in a decrease in the steady-state level of estrogen receptor protein by approximately 70-80%. The effect of gp30 on the concentration of ER was independent of serum in the media and was not inhibited by an epidermal growth factor receptor blocking antibody. In addition to the effect on ER protein, gp30 decreased the steady-state level of ER messenger RNA. Transcription run on experiments demonstrated that the decrease in ER expression was mediated by a decrease in ER gene transcription. The effect of gp30 on estrogen receptor activity was also investigated in this study. Treatment of cells with gp30 blocked estradiol induction of progesterone receptor. Inhibition was observed at the level of progesterone receptor protein, messenger RNA, and gene transcription. gp30 also blocked estradiol induction of pS2 gene transcription. In addition to its effects on progesterone receptor and pS2, gp30 blocked activation of an estrogen response element in a transient transfection assay and inhibited ER binding to its response element in a DNA mobility shift assay, suggesting a direct effect on the estrogen receptor. The effects of gp30 on estrogen receptor concentration and activity were independent of the level of erbB-2 and erbB-4 in the cell. These data show that gp30 regulates the concentration of ER and modulates ER activity.
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PMID:Regulation of estrogen receptor concentration and activity by an erbB/HER ligand in breast carcinoma cell lines. 882 92

Two new immunoenzymatic assays for c-erbB-2 oncoprotein and epidermal growth factor receptor (EGF-R) (Oncogene Science) in human breast cancer were validated. Correlations between these assays and some clinical and biological parameters were also studied. The repeatability and reproducibility of standard curves for the two methods gave a coefficient of variation (CV) of less than 4% and about 10% respectively. The accuracy of c-erbB-2 oncoprotein and EGF-R assays was examined by using dilution and recovery tests throughout the standard curves. The linear relations between theoretical and measured values, for these tests, had slopes close to 1 and an intercept near 0. The median value for EGF-R, measured on solubilized membranes of 290 primary tumors, was 0.12 fmol/micrograms protein, the mean value was 0.37 (range 0 to 35.7). For c-erbB-2 oncoprotein, the median value, measured using the same population, was 2.75 human neu unit/micrograms protein, the mean value was 7.85 (range 1 to 125). There was an inverse relationship between EGF-R values and those for the estrogen receptor (ER), progesterone receptor and pS2 protein as well as menopausal status. C-erbB-2 oncoprotein concentrations were positively correlated with ER, pS2 protein and cathepsin D. Furthermore, a significant positive correlation was observed between EGF-R levels and c-erbB-2 oncoprotein levels. In conclusion, immunoenzymatic assays of EGF-R and c-erbB-2 oncoprotein are easy to use, sensitive and reliable. The accurate standardisation of immunoenzymatic assays could contribute to the clinical use of EGF-R and c-erbB-2 oncoprotein as prognostic factors in breast cancer.
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PMID:[Immunoenzymatic assays of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer: correlation with clinical and biological parameters]. 888 58

Expression of the calcium-dependent cell-cell adhesion molecule E-cadherin has been examined in 187 primary breast carcinomas using an immunohistochemical technique. The pattern and extent of reactivity has been correlated with clinicopathological data including tumour type, grade and lymph node status and with other prognostic parameters including oestrogen receptor (ER) status, expression of c-erbB-2, pS2 protein and epidermal growth factor receptor (EGFR). Two patterns of E-cadherin staining were observed in carcinomas, membrane reactivity and a diffuse cytoplasmic staining. A marked difference in expression of E-cadherin was observed between infiltrating lobular carcinomas (ILC) and infiltrating ductal carcinomas (IDC), the former showing complete loss of membrane staining, whereas 93% of IDC retained some level of expression. In IDC reactivity was not related to tumour grade but there was a significant association between reduced membrane levels of E-cadherin and the presence of lymph node metastasis, and a highly significant correlation between the presence of cytoplasmic E-cadherin and metastasis. A significant relationship was also demonstrated between reduced E-cadherin reactivity and expression of EGFR. These findings emphasise the complexity of control of E-cadherin in breast carcinomas and provide evidence of a link between membrane signalling pathways and modulation of E-cadherin expression.
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PMID:E-cadherin relates to EGFR expression and lymph node metastasis in primary breast carcinoma. 888 10

The present study attempts to clarify the specific contribution of cathepsin D (CD) and pS2 to the progression of breast cancer (BC) by examining the relationship between these two factors and TNM status, tumour grade, estradiol receptors (ER) and the prognosis factors epidermal growth factor receptor (EGFR) and neu amplification in a group of 270 BC patients. CD and pS2 were determined by an immunoradiometric procedure in tumour cytosols obtained for ER. Neu amplifications were evaluated by dot-blot, in tumour DNA. EGFR was determined in membrane tumour preparations obtained from ER cytosols by a two-point radiometric saturation assay. CD is basically related to bad prognosis factors and has a direct correlation with tumour size (P = 0.025) and EGFR content (P = 0.007) and is associated with the presence of metastases (P = 0.000). pS2 is mostly related to good prognosis factors and showed an inverse correlation with the Scarff-Bloom Index (P = 0.011) and a direct correlation with ER content (P = 0.014). Finally, pS2 and CD also showed a strong mutual association (P = 0.009) and the fact that both correlated with ER content confirms in tumours the experimental finding that they are estrogen-induced proteins.
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PMID:Specific oncological contribution of cathepsin D and pS2 in human breast cancer: their relationship with TNM status, estradiol receptors, epidermal growth factor receptor and neu amplification. 892 Feb 30


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