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)

Amplification and enhanced expression of the erbB2/HER-2/neu gene has been associated with an increased growth rate and poor prognosis of human breast cancer. We have studied the relationship between erbB2 expression and the regulation of cell growth by estrogen and anti-estrogens in the human breast cancer cell line ZR-75-1 in vitro and in athymic nude mice, pS2 being used as a marker gene for estrogen-stimulated gene expression. Only low amounts of erbB2 mRNA were seen in the cells grown in vitro in the presence of estrogen which stimulated the cells to proliferate rapidly and induced the expression of pS2 mRNA. Upon hormone withdrawal, erbB2 mRNA and protein increased, while pS2 mRNA declined to an undetectable level and cell proliferation slowed down. Opposite but more rapid changes were observed upon estrogen addition. The anti-estrogens toremifene and tamoxifen inhibited estrogen induction of pS2 expression, down-regulation of erbB2 expression and proliferation of the ZR-75-I cells in a concentration-dependent manner. Similar results were obtained in nude mice. ZR-75-I cells formed tumors only in mice carrying estrogen pellets. In these tumors little erbB2 mRNA was seen. Concomitant administration of toremifene or tamoxifen increased erbB2 mRNA and abolished pS2 mRNA. Our results show that enhanced expression of erbB2 is associated with hormone deprivation and growth arrest of the estrogen-dependent breast cancer cell line ZR-75-I. Thus, in mammary epithelial cells, erbB2 may have important estrogen-regulated functions which are not related to cell proliferation.
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PMID:Estrogen suppression of erbB2 expression is associated with increased growth rate of ZR-75-1 human breast cancer cells in vitro and in nude mice. 168 Aug 17

Antagonists of steroid hormones are clinically important in the management of breast cancer. However, the duration of response is limited due to the development of hormone-independent tumors in virtually all cases. In an attempt to obtain insight into the mechanisms underlying antiestrogen resistance, the consequences of epigenetic changes in gene expression were studied in vitro. Estrogen-dependent ZR-75-1 human breast cancer cells were treated with 5-azacytidine, an inhibitor of DNA methylation, and cultured in the absence of estradiol or in the presence of antiestrogens. Estrogen-independent cell colonies developed within 3 weeks at high frequency in 5-azacytidine-treated cultures (0.7 x 10(-3), in contrast to control cultures (< or = 10(-8). The derived cells (ZR/AZA) were resistant to 4-hydroxytamoxifen and ICI 164,384, independent of the selection protocol, but had lost the ability to grow anchorage-independent. Whereas expression of estrogen receptor, progesterone receptor, and pS2 were down-regulated, expression of epidermal growth factor (EGF) receptor and HER2/neu were increased in ZR/AZA cells. In contrast to the stable altered expression patterns of estrogen receptor and EGF receptor, transient keratin 7 expression was observed. Transforming growth factor-alpha mRNA was identified in ZR-75-1 cells and ZR/AZA cells and EGF-like peptides were secreted in the culture medium. Proliferation of ZR/AZA cells could be partially inhibited with an EGF receptor-blocking antibody. Presence of both growth factor receptors and possible ligands suggests the development of an autocrine growth mechanism. Our data show that epigenetic alterations of gene expression result in rapid progression of breast cancer cells to hormone independence.
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PMID:Induction of estrogen independence of ZR-75-1 human breast cancer cells by epigenetic alterations. 753 60

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

Amplification of c-myc and c-erb beta-2 (HER-2/neu) proto-oncogenes were analyzed in breast cancer tissues obtained from 100 patients without lymph node involvement (N-). An amplification of the c-myc gene was detected in four cases and a c-erb beta-2 (HER-2/neu) amplification in eight cases. The frequency of these abnormalities were compared to classical prognostic parameters as well as to new biological prognostic markers (cellular cycle, cathepsin-D and pS2 protein). Most of altered tumors were associated to some classical poor prognostic factors such as: steroid receptor-negative tumors, poorly differentiated tumors, high histoprognostic grade and tumor cell density. In contrast, no relation was found with new biological parameters. The analyses of these data in relation to clinical evolution will be of interest to evaluate their prognostic value.
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PMID:[Amplification of c-myc and c-erbbeta-2(HER-2/neu) in breast cancer without axillary lymph node metastasis: correlation with other prognostic parameters]. 770 67

Immunophenotypes of mammary (MPD) and extramammary Paget's disease (EPD) are still not well understood. Thirty-four formalin-fixed paraffin-embedded tissue sections from 33 patients with 6 MPD and 28 EPD were studied immunohistochemically with the use of polyclonal c-erbB-2 and pS2 antisera, and monoclonal nm23, B6.2, GCDFP-15, and p53 antibodies. Cases of MPD expressed a high incidence of c-erbB-2 and nm23 compared with those of EPD (100% vs. 29%; p < 0.01, and 83% vs. 29%; p < 0.05, respectively). Although high expression of B6.2 (> 83%) and moderate expression of GCDFP-15 (33-39%), pS2 (33-46%) and p53 (39-50%) were seen, the positivity was not significantly different between MPD and EPD. These findings indicate that MPD and EPD share immunohistochemical features but partially differ in their patterns of antigen expression.
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PMID:Immunohistochemical study of mammary and extramammary Paget's disease. 776 23

The pathological and biological features of a consecutive series of impalpable invasive breast carcinoma, detected by mammography in the prevalent round of the breast screening programme, have been compared with a clinically presenting group of carcinomas in age-matched patients. There was a significantly higher prevalence of tubular carcinomas as well-differentiated infiltrating ductal carcinomas in the mammographically detected group, and a lower prevalence of poorly differentiated infiltrating ductal carcinomas. Lymph node metastasis was found in 6.5% of the impalpable group compared with 53% of the clinical group. The prevalence of oestrogen receptor was much higher in the impalpable group (96%) than in the control group (67%), although there were no significant differences for progesterone receptor. The prevalence of pS2 was also much higher in the impalpable group, as was cathepsin D. This finding is surprising in view of the reported relationship between cathepsin D and poorer survival. p53 and c-erb-2 proteins were detectable in fewer impalpable carcinomas. The mean MIBI (Ki-67) index was lower in the impalpable group (11.6) than in the clinical group (15.25). Within the mammographically detected group there was a significant difference in the MIBI index between tubular carcinomas and the different grades of infiltrating ductal carcinomas, with a wide range in each category but no association with size. The impalpable carcinomas detected by mammography differ from clinically presenting carcinomas in many ways, raising the question of whether a proportion or all would progress (dedifferentiate) with time.
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PMID:Pathological and biological features of mammographically detected invasive breast carcinomas. 759 62

A series of 200 breast carcinomas was investigated on frozen sections using PAb 1801 p53 monoclonal antibody and streptavidin biotin peroxidase complex. Densitometric analysis of the immunoprecipitates was assessed by processing digitized microscopic images. p53 was observed in the nucleus of 48% of the tumors. Some tumors (14 of 91) tested in parallel on paraffin sections were negative, although positive on frozen sections. Image analysis showed that the surfaces positive with anti-p53 and the staining intensity were decreased (P < .01) on paraffin sections. The p53 tumor expression was independent of patient age, tumor size, axillary lymph node status, HER-2/neu and cathepsin D expression, and nuclear morphometric parameters. However, p53 correlated with high histological grade (P < .01), lack of estrogen receptor (ER) (P = .0015) and progesterone (PR) (P = .0065) antigenic sites, pS2 detection (P = .03), high Ki-67 immunoreactivity (P = .018), large silver-stained nucleolar organizer region (AgNOR) nuclear surface ratio (P < .02), and degree of hyperploidy (P < .03), and was more often observed in the comedocarcinomas. The results suggest that p53 expression in breast carcinomas is not a totally independent prognostic indicator and that the clinical relevance and prognostic significance of p53 expression in breast carcinomas can be reliably assessed provided that the procedures are standardized, particularly with regard to the use of frozen sections and image analysis processing of the immunodetection.
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PMID:p53 quantitative immunocytochemical analysis in breast carcinomas. 786 46

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

Breast cancer is a complex but increasingly well-understood disease. Clearly, multiple alterations from normal mammary cells are required to achieve a transformed phenotype. Furthermore, there may be several possible alterations within broad categories that will produce the transformations leading to the malignant state. The specific set of alterations within a given cancer may thus provide necessary information about how it is unique and how it may best be treated. Several of the newer biologic markers of breast cancer may provide very specific treatment information. erbB-2 may predict for improved response to doxorubicin, rather than CMF. hsp 27 may predict for failure of doxorubicin. pS2 or EGFR may provide supplemental information predicting response to hormonal therapy. Each of these variables has strong evidence to support its use in this manner, but that evidence has been obtained on limited numbers of patients treated in a limited number of ways. The most established markers, with multiple studies indicating their prognostic benefit, are erbB-2, cathepsin D, and proliferation markers. Of the several proliferation markers there may be no one choice that is best. However, very clearly, any marker must be carefully assessed for appropriate cut-off values, and cut-off values established by one cohort of patients should be verified against another cohort of patients. The oncoproteins associated with cell cycle regulation (cyclin D, p53, Rb, and c-myc) have shown strong promise of providing important prognostic information. The limited studies to date indicate that these markers are independent of one another. Cell cycle regulation may be an area in which any defect may serve to deregulate the cell, and therefore several defects in one cell would be unlikely. The specific nature of the defect in a given cancer may be very important. With the advent of immunohistochemical methods to measure most of the markers, more information may become available. Finally, the burgeoning area of tumor-stromal interactions is replete with potentially important markers of cancer prognosis. The growth factors, which are marginally a part of this area owing to the probable importance of paracrine effects on cancer cell growth, have progressively developed a body of literature supporting their prognostic potential. However, they have rarely been studied in conjunction with the other aspects of tumor-stromal cooperation. The markers of metastatic potential, nm23 and angiogenesis, have been shown in small cohorts to have considerable prognostic import.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Overview of the biologic markers of breast cancer. 815 Jul 84

Seventy-four post menopausal patients with primary non-metastatic invasive ductal carcinomas of the breast were first treated with tamoxifen alone (30 mg p.o. daily) for 5 months. To study changes induced by tamoxifen, core biopsies before treatment and surgical specimens after hormonal therapy were assayed by immunohistochemistry for oestrogen (ER) and progesterone receptors (PR), pS2, GSTpi and c-erbB2. After tamoxifen, ER and PR significantly decreased in 60 and 44 cases respectively, whereas 11 and 19 cases showed no variation and 2 and 11 cases showed an increase (P<10(-4)). GSTpi and pS2 showed a significant increase in 43 and 41 cases, a decrease in 2 and 21 cases and no variation in 29 and 12 cases (P<10(-4) and P=0.04 respectively). c-erbB-2 showed no significant variation under tamoxifen, increased in only three cases and decreased in 13 cases. No relation was found between these variations and efficiency of hormone therapy. Our results allow a better knowledge of protein expression modifications occurring in breast cancer cells under tamoxifen therapy. They are also more consistent with clone selection rather than with phenotype modification.
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PMID:Variation of hormonal receptor, pS2, c-erbB-2 and GSTpi contents in breast carcinomas under tamoxifen: a study of 74 cases. 861 73


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