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)

A hormone-independent but hormone-responsive subpopulation (MCF7/MIII) of the hormone-dependent MCF-7 human breast cancer cell line (R. Clarke et al., Proc. Natl. Acad. Sci. USA 86: 3649-3653, 1989) was further passaged in ovariectomized nude mice and re-established in vitro as the continuous cell line MCF7/LCC1. The lag time to the appearance of proliferating tumors in ovariectomized animals is significantly reduced in MCF7/LCC1 when compared with MCF7/MIII cells. In gel denaturation/renaturation analysis of tumor, genomic DNA does not reveal significant differences in the pattern of detectable DNA amplifications between parent MCF-7 cells and MCF7/LCC1 cells. In the absence of estrogen, steady-state levels of phosphoinositol turnover are similar in both MCF-7 and MCF7/LCC1 cells, but turnover is increased by estrogen only in MCF-7 cells. MCF7/MIII and MCF7/LCC1, but not MCF-7 cells, express a high baseline level of the estrogen-regulated pS2 mRNA. The baseline level of expression of progesterone receptor protein, but not mRNA, is higher in MCF7/LCC1 when compared with either MCF-7 or early passage MCF7/MIII cells. However, while the estrogen receptor is also an estrogen-regulated gene, MCF7/MIII and MCF7/LCC1 cells retain estrogen receptor levels equivalent to the parental MCF-7 cells. These data indicate that progression to hormone independence can occur without major gene amplifications or a high constitutive induction of phosphoinositide metabolism. Thus, DNA amplifications may be acquired during the early initiation and/or promotional events of carcinogenesis. Significantly, acquisition of a hormone-independent but responsive phenotype in human breast cancer is associated with perturbations in the expression of specific estrogen-regulated genes.
Cancer Res 1993 Jan 15
PMID:Acquisition of hormone-independent growth in MCF-7 cells is accompanied by increased expression of estrogen-regulated genes but without detectable DNA amplifications. 838 Feb 54

The expression of pS2 was examined histochemically in paraffin sections taken from biopsy material from patients diagnosed with ductal carcinoma in situ (DCIS). Often intense immunoreactivity, to an anti-pS2 monoclonal antibody, was observed in comedo, solid, cribriform and micropapillary types of DCIS, with significant positivity found in 63-67% of cases. In 15 samples analysed, we found a good correlation between pS2 expression and presence of progesterone receptor positive cells, but not with estrogen receptor. There was only a limited degree of correspondence between the cells staining with these anti-sera. Some pS2 positive cells were also seen in normal acini in areas adjacent to cancer but much less frequently in sections of normal breast from reduction mammoplasty. Most normal areas were negative, as were cysts. In benign proliferative conditions (seen in sections with and without DCIS) such as adenosis, sclerosing adenosis, mild and florid ductal epithelial hyperplasia, significant pS2 positivity was seen in about 50% of cases. These results suggest that there is a progressive increase in pS2 from normal to benign to cancer cells and that this gene is expressed in both the invasive and pre-invasive forms of breast cancer.
Br J Cancer 1993 Apr
PMID:Immunohistochemical localisation of pS2 protein in ductal carcinoma in situ and benign lesions of the breast. 838 77

The expression of four oestrogen-responsive genes in 118 immunohistochemically defined primary breast tumours has been determined by northern analysis. While all the genes are induced by oestrogen in oestrogen receptor (ER)-positive cell lines, their behaviour is different in breast tumour biopsies. This behaviour can be divided into two groups; the first containing the genes, pLIV1 and pLIV2 (pS2), which both show a significant association with ER status (P = 0.001) and a corresponding inverse relationship with epidermal growth factor receptors (EGFR) (P = 0.01 and P = 0.08, respectively). In addition, the mRNA levels of both pLIV1 and pS2 are greater in ER-positive compared to ER-negative disease (P = 0.001). While a small number of ER-negative tumours were positive for either pLIV1 (12%) or pS2 (9%), we failed to observe co-expression of pLIV1 and pS2 in ER-negative disease. In ER-positive disease, four tumour populations were identified; ER+pLIV1-pS2-, ER+pLIV1-pS2+, ER+pLIV1+pS2- and ER+pLIV1+pS2+. Interestingly, the levels of pLIV1 and pS2 when co-expressed were significantly greater in ER+pLIV1+pS2+ tumours compared to either of the ER+pLIV1+pS2- (P = 0.03) or ER+pLIV1-pS2+ (P = 0.01) mixed phenotypes. Unlike pLIV1 and pS2, pSYD3 and pSYD8 belong to a group of genes which are expressed in the majority of tumours regardless of ER and EGFR status. However, lower pSYD8 mRNA levels were detected in moderately EGFR-positive disease (P = 0.06) while both pSYD3 positivity (P = 0.01) and mRNA levels (P = 0.001) were increased in highly proliferating tumours as shown by Ki67 immunostaining. These genes provide additional markers which, in conjunction with other parameters, may help to determine the likelihood of a given tumour to respond to endocrine therapy.
Eur J Cancer 1993
PMID:The role of four oestrogen-responsive genes, pLIV1, pS2, pSYD3 and pSYD8, in predicting responsiveness to endocrine therapy in primary breast cancer. 839 76

A novel oestrogen-responsive breast-tumour cell line, EFF-3, has been established from a pleural exudate of a patient with metastatic breast cancer. The cells show morphological and immunohistochemical features consistent with their origin from a metastatic breast carcinoma. The cells aggregate and form sheets in culture, and electron microscopy confirms the presence of cell-surface microvilli and intercellular tight junctions. The epithelial origin of EFF-3 cells was confirmed by their expression of low-molecular-weight cytokeratins and carcinoembryonic antigen. The karyotype of the cells is markedly abnormal and there are large numbers of structurally abnormal chromosomes. EFF-3 cells express oestrogen receptor, oestrogen-receptor mRNA, their growth is oestrogen-responsive, and specific genes are regulated by oestrogens. The pNR-2/pS2 and pNR-25 oestrogen-regulated mRNAs are induced 15- and 13-fold respectively by oestrogen, whereas the oestrogen-receptor and cathepsin D mRNAs are not regulated. This pattern of regulation differs from that reported previously for other cell lines. The EFF-3 cell line should be useful for studying the mechanisms involved in oestrogen-stimulated proliferation and the factors determining the regulation of specific genes by oestrogens.
Int J Cancer 1993 Feb 01
PMID:Isolation and characterization of an oestrogen-responsive breast-cancer cell line, EFF-3. 842 92

In order to isolate additional markers of oestrogen responsiveness in breast cancer and to study the mechanisms associated with the development of endocrine resistance, we have searched for oestrogen regulated genes. Differential hybridisation analysis of a cDNA library prepared from oestrogen-stimulated T-47D cells has led to the isolation of a sequence (pMGT1) whose expression is repressed (up to 8-fold) by oestrogen (10(-9) mol/l) and represents the first down-regulated gene to be identified by this methodology. Further studies of pMGT1 expression in MCF-7 cells has revealed that the pure antioestrogens, ICI164384 (10(-7) mol/l) and ICI182780 (10(-7) mol/l) and the antiprogestin Ru38486 (10(-7) mol/l), increase pMGT1 mRNA levels by approximately 40-50-fold relative to the value seen in cells exposed to oestrogens. Under the same conditions, pS2(pLIV2), a gene which is positively regulated by oestradiol, was almost undetectable. Significantly, both tamoxifen (10(-7) mol/l), and 4-hydroxytamoxifen (10(-7) mol/l), failed to increase pMGT1 mRNA levels. Since cell culture studies have indicated that ICI164384 and ICI182780 are more effective than tamoxifen and 4-hydroxytamoxifen at inhibiting the growth of MCF-7 cells by mechanisms that lower their viability and sensitivity to growth factors, it is feasible that pMGT1 plays a central role in mediating these events and instigating pathways associated with cell death.
Eur J Cancer 1993
PMID:Isolation of pMGT1: a gene that is repressed by oestrogen and increased by antioestrogens and antiprogestins. 847 35

Estradiol levels in breast tumors from post-menopausal women are similar to those in pre-menopausal women even though plasma estrogens are much lower after the menopause. In situ estrogen production by the tumor provides a potential means of maintaining high estradiol levels in post-menopausal breast cancer tissue. The estrone sulfatase pathway has been proposed as the mediator of in situ estrogen production. A number of studies suggest that estrone sulfate may be converted into estradiol in breast tumors via the catalytic activity of estrone sulfatase and 17 beta-hydroxysteroid dehydrogenase. However, these studies used pharmacologic levels of estrogen sulfates and have not shown that physiologic levels can support biologic effects. Accordingly, the present study examined the dose relationship of estrone sulfate to a variety of biologic endpoints in MCF-7 breast cancer cells in culture. These cells converted physiologic concentrations of estrone sulfate to quantities of free estradiol capable of stimulating cell growth. Under these conditions, the nuclear steroids observed were free estrone and estradiol. Increase in cell number after 6 days of exposure to steroid required 100 nM estrone sulfate. However, S-phase, a more sensitive measure of cell proliferation, was stimulated by 0.1 nM estrone sulfate, a clearly physiologic concentration. Stimulation of estrogen-dependent protein markers such as pS2 and progesterone receptor required much higher concentrations of estrone sulfate. These effects were mediated through the estrogen receptor since the pure anti-estrogen, ICI 164384, blocked all effects produced by estrone sulfate. While it has been suggested that anti-estrogens may partly exert their effects by inhibition of sulfatase and 17 beta-hydroxysteroid dehydrogenase, this did not occur under our experimental conditions. These data provide evidence of the relevance of the estrone sulfatase pathway since biologic effects can be demonstrated in response to physiologic concentrations of estrone sulfate.
Int J Cancer 1993 Apr 22
PMID:Estrone sulfate promotes human breast cancer cell replication and nuclear uptake of estradiol in MCF-7 cell cultures. 847 38

Women who have breast cysts with intracystic Na+/K+ < 3 may have a higher risk of developing breast cancer than women who have breast cysts with intracystic Na+/K+ > 3. In this study wide-ranging intracystic concentrations of cathepsin D and pS2 (oestrogen inducible proteins/polypeptides) as well as oestradiol were found. The concentrations of cathepsin D and oestradiol were significantly higher in the low electrolyte ratio cyst group than in the high electrolyte ratio cyst group. No significant difference was found between pS2 concentrations in the two groups. The significantly higher intracystic concentrations of cathepsin D, a mitogenic lysosomal endopeptidase and oestradiol in the low electrolyte ratio group may partly provide an explanation for the higher risk of breast cancer which has been observed in this group of women.
Cancer Lett 1993 Apr 15
PMID:Relationships between oestrogen-inducible proteins, oestradiol and electrolyte ratio in breast cyst fluid. 848 90

A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficulty accurately to predict the response to treatment. A valuable prognostic factor can be a poor predictive factor for response, and vice versa. High tumor levels of ER, PgR, AR and pS2 predict a relatively good response to endocrine therapy, while EGF-R positively, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high uPA levels indicate a high chance of poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and HER2/neu amplification predict a good response to therapy in metastatic disease, while MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low-risk patients, type of systemic treatment, and as targets for new treatment modalities.
Cancer Treat Rev 1993 Apr
PMID:Cell biological factors associated with the response of breast cancer to systemic treatment. 848 34

Histological sections obtained from 70 patients with breast cancer, all of whom had received endocrine therapy for metastatic or locally advanced disease, were assessed for specific immunocytochemical staining of oestrogen receptor and the oestrogen-induced protein pS2. There was also sufficient material from 25 patients for an assessment of progesterone receptor by immunocytochemistry. We found that, when using a "cut-off" point of 50% for ER and PR, and of 25% for pS2, ER was positive in 22/29 responders and in 12/41 non-responders, and thus was significantly associated with response to endocrine therapy. Similarly, in those subjects in whom PR was measured, PR was positive in 5/14 responders and negative in all 11 non-responders, again being significantly correlated with response. However, pS2 did not relate to response, being only positive in 10/29 responders and negative in 26/41 non-responders. The different response categories varied in their "percentage of positivity" as determined by the 2 tests. Thus, for ER and pS2 we observed: complete response--71% for ER compared with 14% for pS2; partial response--77% compared with 41%; stable disease--36% compared with 64%; and progressive disease--27% compared with 27%. We conclude that at the present time ER appears to be the most reliable indicator for predicting response to endocrine therapy in patients with breast cancer.
Int J Cancer 1993 Jun 19
PMID:Prediction of response to endocrine therapy in breast cancer using immunocytochemical assays for pS2, oestrogen receptor and progesterone receptor. 851 53

Competitive polymerase chain reaction assays have been developed for the quantitation of oestrogen receptor mRNA and two oestrogen-regulated mRNAs (progesterone receptor and pNR-2/pS2) in breast cancer cells. These assays are more sensitive than traditional hybridisation techniques, do not require the use of radioisotopes, measure absolute amounts of messenger RNAs and can be used to measure the expression of mRNAs in small numbers of tumour cells obtained by fine-needle aspiration (FNA). These assays should prove useful for predicting the hormone responsiveness of breast cancer from tumour cells obtained by FNA at diagnosis and could be particularly useful in the management of elderly/frail patients who receive primary tamoxifen, or in other patients for whom tumour tissue for standard biochemical measurements is not available.
Br J Cancer 1995 Dec
PMID:Determination of oestrogen responsiveness of breast cancer by competitive reverse transcription-polymerase chain reaction. 851 55


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