Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel estrogen receptor mRNA splice variant which lacks the entire exon 5 and part of exon 4 and 6 was identified using reverse transcription PCR in human breast carcinomas. The variant was translated in vitro and produced a protein of approximately Mr 31000 which lacked the ligand binding domain. The binding of the variant estrogen receptor (ER) to a synthetic estrogen-responsive element (ERE) was compared with that of the wild-type ER (wtER). The variant ER bound weakly to the synthetic ERE, both in the presence and absence of estradiol, whilst the wtER bound strongly in the absence and the presence of estradiol. When wtER and variant ER were simultaneously translated in vitro, no heterodimerization was observed using band shift assay. Addition of increasing amounts of variant ER protein to the wtER in the ERE binding reaction showed that the variant protein competed with the binding of the wtER to the synthetic ERE. Furthermore, variant ER are not transcriptionally active. The variant was also expressed in 96% of the 102 breast tumours analysed, of which 62 were tamoxifen-resistant tumours. The expression of this variant was significantly higher (relative to ER) in untreated ER-positive breast tumours which were both progesterone receptor (PgR) negative and pS2 negative phenotype.
 ...
PMID:A novel estrogen receptor variant mRNA lacking exons 4 to 6 in breast carcinoma. 944 45

The aim of this study was to add to existing information on the effects of certain tumour markers expressed by breast cancers on tumour malignancy as evidenced by size of primary and occurrence of lymph node invasion. One hundred freshly resected breast cancers were examined by immunocytochemical staining of imprint smears for Cathepsin D and pS2. Oestrogen receptor (ER) and progesterone receptor (PR) were tested for by dextrose-coated charcoal (DCC) assay and the results correlated with tumour size, histology and presence or absence of lymph node metastases at the time of surgery using chi(2) analysis. A significant positive correlation was demonstrated between Cathepsin D positivity and ER, PR and pS2 positivity. In tumours < 2 cm in diameter at surgery a positive correlation was observed between Cathepsin D positivity and the presence of lymph node metastases. The findings support the hypothesis that Cathepsin D may promote early metastasis, possibly by its proteolytic activity.
 ...
PMID:Expression of cathepsin D and pS2 in imprint smears of breast carcinoma. 971 Jun 94

Mucinous carcinoma may present at various sites, including the breast and the gastrointestinal tract. Rarely, such tumors arise within the skin. Comparatively, breast lesions are relatively common and usually associated with a good prognosis. When pure, they are typically estrogen (ER) and progesterone receptor (PR) positive and responsive to tamoxifen. The authors studied 12 mucinous carcinomas of the skin and compared the morphology with that of typical mammary lesions. The authors also evaluated for expression of estrogen receptor, progesterone receptor, and the mucus-associated peptides of the trefoil factor family (TFF), TFF1 (formerly pS2) and TFF2 (formerly SP), using immunohistochemistry. The localization of mRNAs for TFF1, TFF2, and TFF3 (formally ITF) was also studied in a subset of three tumors, using in-situ hybridization with S35 labeled riboprobes. The Grimelius stain was used to look for evidence of neuroendocrine differentiation. Eight resembled type A mucinous carcinomas of the breast, two resembled type B, and one had composite features. The 12th was a papillary neoplasm. The two type B tumors exhibited argyrophilia. All showed strong nuclear staining with the estrogen receptor antibody but a more varied pattern with antibodies to progesterone receptor and TFF1. None labeled for TFF2. The detection of TFF1 in mammalian skin is a novel finding. Cutaneous mucinous carcinoma shows strong similarities to its mammary counterpart, including expression of estrogen receptor, TFF1, and TFF3 mRNA. These observations suggest that some mucinous carcinomas of the skin might respond to antiestrogenic therapies.
 ...
PMID:Primary mucinous carcinomas of the skin express TFF1, TFF3, estrogen receptor, and progesterone receptors. 973 46

The histogenesis of phyllodes tumour (PT) and that of fibroadenoma (FA) of the breast appear to be closely related. FA is thought to be hormonally responsive, while the hormone-responsiveness of PT is uncertain. To gain insight into hormone-responsiveness of PT, we performed immunohistochemical analysis of oestrogen-regulated pS2 and androgen-regulated prostate-specific antigen (PSA) protein expression and also of oestrogen receptor (ER), progesterone receptor (PgR) and androgen receptor (AR) expression in paraffin sections obtained from 50 female PT patients. Paraffin sections taken from 50 female fibroadenoma (FA) patients were analysed for comparison. ER, PgR, pS2, AR and PSA expression were detected in 32%, 96%, 20%, 98% and 4.0% of PT sections and in 28%, 96%, 42%, 80% and 10% of FA sections, respectively. No correlations were detected among ER, PgR and pS2 expression or between AR and PSA expression in PT or FA sections. PgR expression was significantly associated with AR expression in PT (P<0.0001). The present investigations indicate that PT and FA have almost similar hormone receptor status. However, different positivities of pS2 expression suggest that oestrogen-responsiveness may differ between PT and FA. In addition, a wide-ranging co-expression of AR and PgR in PT sections suggests that these receptors may play an important part in the proliferation, although the functional significance of these receptors should be elucidated.
 ...
PMID:Immunohistochemical study of hormone receptor and hormone-regulated protein expression in phyllodes tumour: comparison with fibroadenoma. 980 32

We describe the development and use of a sensitive reverse transcription-PCR (RT-PCR) procedure to detect novel estrogen-regulated gene expression in small clinical breast cancer samples, in which such study would be extremely difficult by any other molecular or immunocytochemical means. Assay optimization for pLIV1, estrogen receptors (ERs), progesterone receptors, and pS2 gene products was carried out on 50 primary breast cancers for which comparative Northern analysis and immunocytochemical data were available. Using 27 amplification cycles and a 0.5 microM primer concentration, varying expressions of the gene products were recorded simultaneously with a constant densitometric signal for a coamplified endogenous control gene (alpha-actin). Good concordances were subsequently observed between pLIV1 status generated by RT-PCR and both Northern analysis (P = 0.002) and ER status by immunocytochemistry (P = 0.0244). Agreement was also noted between ER (P = 0.002), progesterone receptor (P = 0.0005), and pS2 (P = 0. 0023) RT-PCR and immunocytochemical methodologies. The RT-PCR assays were then applied to 10 needle core trucut biopsies in which similar relationships were obtained. Our results justify the future use of this RT-PCR methodology to examine new estrogen-regulated genes in small breast cancer samples, and it is envisaged that this technology will prove invaluable in many future breast cancer studies.
 ...
PMID:Use of reverse transcription-polymerase chain reaction methodology to detect estrogen-regulated gene expression in small breast cancer specimens. 981 11

There is controversy concerning the prognosis of breast cancers arising in women carrying loss of function mutations in the breast cancer susceptibility genes BRCA1 and BRCA2. This study was carried out to assess the likely hormone dependence of this group of tumours in comparison with an age and grade matched group of control sporadic tumours. We used quantitative immunohistochemical analysis for the oestrogen receptor (ER), progesterone receptor (PgR), cyclin D1 and pS2 on sections of primary tumours and ductal carcinoma in situ (DCIS). Expression of PgR (P < 0.05) and cyclin D1 (P < 0.01) was low in the BRCA1- and BRCA2-associated cancers compared with sporadic cases. The low frequency of expression of ER (9/40), PgR (2/40) cyclin D1 (5/36) and pS2 (5/36) in the familial tumours indicates that the majority of such tumours will be oestrogen insensitive and unlikely to respond to hormonal manipulation even at the in situ stage in their evolution. The low level of PgR (2/40 cases) suggests that there may be some abnormality of transactivating function of the ER in these tumours.
 ...
PMID:Predicted anti-oestrogen resistance in BRCA-associated familial breast cancers. 989 52

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds induce a broad spectrum of biochemical and toxic responses and disrupt multiple endocrine pathways. Research in this laboratory has focused on characterizing aryl hydrocarbon receptor (AhR)-mediated antiestrogenicity in the rodent uterus and mammary and in human breast cancer cells. TCDD inhibits multiple estrogen (E2)-induced responses in these tissues including development or growth of human mammary and endometrial cancer cells, carcinogen-induced mammary cancer in rats, and mammary cancer in mice bearing breast cancer cell xenografts. The mechanisms of AhR-mediated antiestrogenicity are complex; however, studies on the molecular biology of cross-talk between the AhR and estrogen-receptor (ER) signaling pathways have been initiated using several E2-regulated genes as models. The results indicate that the nuclear AhR complex targets specific genomic core inhibitory dioxin responsive elements (iDREs) in promoter regions of some E2-responsive target genes to inhibit hormone-induced transactivation. The pS2, cathepsin and c-fos genes have functional iDREs, whereas the iDRE in the progesterone receptor gene promoter was not functional. Research has also focused on development of AhR-based antiestrogens which inhibit mammary tumor development and growth but do not exhibit prototypical AhR-induced toxic responses.
 ...
PMID:Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms. 1002 76

Endocrine treatments for human breast cancer have been based largely upon the removal of estrogenic stimuli. The regression of tumors after estrogen deprivation has generally been characterized as being due to reduced proliferation but more recently has been recognized to also involve increased apoptosis. The aim of our experiments was to define the associated changes in certain proliferation- and cell death-related biological parameters after hormone withdrawal from estrogen-dependent MCF-7 xenografts in athymic nude mice using immunohistochemical techniques. The baseline estrogen receptor (ER) level of this MCF-7 xenograft was relatively low (average H score 23) but it was strongly Bcl-2-, PgR- and pS2-positive, indicating the functional integrity of estrogen signaling. Changes in proliferation (Ki-67), apoptosis, ER, progesterone receptor (PgR), cyclin D1, p27kip1, Bcl-2 and Bax expression were assessed during the 2 weeks after estrogen deprivation. ER levels rose markedly after estrogen ablation, whereas PgR levels fell to about 10% of baseline and pS2 levels halved. The proportion of Ki-67-positive cells was unchanged after 24 hr but by day 14 had reduced by about 80%. The normal levels of cyclin D1 also reduced after estrogen withdrawal in contrast to the rapid increase in levels of cyclin-dependent kinase inhibitor p27kip1. This latter increase appeared to occur in advance of the changes in Ki-67. The proportion of apoptotic cells increased from a mean 1.5% at baseline to 2.9% after 3 days and 4.7% after 14 days. There were reductions in both Bcl-2 and Bax staining but these appeared to be greater for Bcl-2, effectively decreasing the Bcl-2/Bax ratio. Our results provide a framework for the use of these parameters as intermediate markers in comparisons of hormonal agents for human breast cancer treatment.
 ...
PMID:Time-related effects of estrogen withdrawal on proliferation- and cell death-related events in MCF-7 xenografts. 1018 36

Primary transcripts of the human estrogen receptor (ER) and progesterone receptor (PR) are subject to a number of alternative splicing events resulting in a range of variant messenger ribonucleic acid species in receptor-positive tissues. Despite in vitro demonstrations of a possible role for some of these variants in hormonal sensitivity, the clinical significance of this process is uncertain. In this study the coexpression of variant ER and PR transcripts has been documented by RT-PCR and Southern blot analysis in a series of receptor-positive breast tumors. In 35 ER-positive tumors, a common profile of variant ER transcripts was present, with all tumors containing the delta2ER and delta7ER, 94% containing the delta4ER, and 83% containing the delta5ER. In 25 of these cases, which were also PR positive, the most highly expressed PR variants, the delta4PR, delta6PR, and delta(4/2)PR, a transcript from which a 126-bp portion of PR exon 4 was deleted, were detected in over 90% of the cases. The alternatively spliced ER variants were expressed at higher relative levels than the PR species, which had mean levels of expression less than 10% that of wild-type PR. The most abundant species was the delta7ER, which was present at levels ranging from 29-83% of the wild type. There was no relationship between the level of delta7ER in individual tumors and the pattern of expression of the estrogen-responsive proteins PR and pS2. The common profile of alternatively spliced ER and PR transcripts in breast tumors means that this feature cannot be used as a discriminator of hormone responsiveness or other clinical end points. Further, the low level of expression of the majority of variant species calls into question their potential for impacting significantly on receptor function.
 ...
PMID:Coexpression of alternatively spliced estrogen and progesterone receptor transcripts in human breast cancer. 1019 81

We compared the oestrogenic and anti-oestrogenic properties of the two well-known phyto-oestrogens, genistein and quercetin, on the oestrogen-sensitive breast cancer cell line MCF-7. Genistein exerted a biphasic effect on growth of MCF-7 cells, stimulating at low and inhibiting at high concentrations, whereas quercetin was only growth inhibitory. At doses which did not inhibit cell growth, respectively 5 and 1 microM, genistein and quercetin counteracted oestrogen- and transforming growth factor-alpha-promoted cell growth stimulation. Furthermore, genistein promoted transcription of the oestrogen-regulated genes pS2 and cathepsin-D, whereas quercetin interfered with the oestrogen-induced expression of the proteins. In in vitro binding experiments, genistein competed with oestradiol for binding to the oestrogen receptor (ER), but quercetin did not. Quercetin and genistein down-regulated cytoplasmic ER levels and promoted a tighter nuclear association of the ER, but only genistein was able to up-regulate progesterone receptor protein levels. In gel mobility assays, ER preincubation with oestradiol or with the two phyto-oestrogens led to the appearance of the same retarded band, excluding differences between the various complexes in binding to the consensus sequence. The data allowed us to conclude that quercetin acts like a pure anti-oestrogen, whereas genistein displays mixed agonist/antagonist properties, and to formulate a hypothesis on the possible mechanism of action of such phyto-oestrogens.
 ...
PMID:The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function. 1037 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>